# NM_000023.4(SGCA):c.163_164del (p.Pro55fs)

https://sugi.bio/variant/sgca-p-pro55fs

## Summary

**SGCA p.Pro55fs (c.163_164del)** is classified **Likely pathogenic** in SGCA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-15). Very rare (popmax 0.00329%, sas); Associated with autosomal recessive limb-girdle muscular dystrophy type 2D.

**At a glance:** Likely pathogenic · review: Single submitter · rsID rs759624003 · 1 submitter · 1 linked condition · very rare (popmax 0.00329%, sas)

## For patients & families {#patients}

This is a change in the SGCA gene that is considered likely disease-causing, submitted by 1 submitter, and is linked to autosomal recessive limb-girdle muscular dystrophy type 2D.

*Reference information, not medical advice, and not a prediction for any individual. A genetic counselor or clinician can interpret what it means for you and your family.*

|  |  |
| --- | --- |
| Typical inheritance (of this condition) | Autosomal recessive |
| Age of onset (of this condition) | Adolescent, Childhood |
| Prevalence | <1 / 1 000 000 (United Kingdom) |
| Clinical trials | 3 registered for this condition — see ClinicalTrials.gov |
| Diagnostic panels | SGCA is a diagnostic-grade gene on 5 Genomics England panels |

**Commonly reported features of Alpha-sarcoglycan-related limb-girdle muscular dystrophy R3** (across patients with this condition; presentation varies — frequencies from Orphanet):

- Achilles tendon contracture — Frequent (79-30%)
- Frequent falls — Frequent (79-30%)
- Waddling gait — Frequent (79-30%)
- Elevated circulating creatine kinase concentration — Frequent (79-30%)
- Hyperlordosis — Frequent (79-30%)
- Gowers sign — Frequent (79-30%)
- Difficulty climbing stairs — Frequent (79-30%)
- Muscular dystrophy — Frequent (79-30%)

**Support & next steps:** [Condition overview & support (NIH GARD)](https://rarediseases.info.nih.gov/diseases/0000438/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [SGCA](https://sugi.bio/atlas/gene/SGCA/) |
| Protein change (HGVS p.) | p.Pro55fs |
| Coding change (HGVS c.) | c.163_164del |
| MANE Select transcript | [NM_000023](https://www.ncbi.nlm.nih.gov/nuccore/NM_000023) |
| dbSNP | [rs759624003](https://www.ncbi.nlm.nih.gov/snp/rs759624003/) |
| Variant type | Deletion |
| Location | chr17:50167586-50167587 (GRCh38) |
| ClinVar | [VCV1724423](https://www.ncbi.nlm.nih.gov/clinvar/variation/1724423/) |

**All HGVS expressions:** `LRG_203:g.6583_6584del`, `LRG_203t1:c.163_164del`, `NC_000017.10:g.48244948_48244949del`, `NC_000017.11:g.50167587_50167588del`, `NG_008889.1:g.6583_6584del`, `NM_000023.4:c.163_164del`, `NM_001135697.3:c.163_164del`, `NR_135553.2:n.199_200del`

## Computational & population evidence {#evidence}

**Concordance:** Mixed / partial computational evidence (see below).

- **Missense predictors (AlphaMissense/REVEL/SaProt) do not apply** to this variant type — they score amino-acid substitutions only. For non-missense variants the computational signal comes from conservation (below), not from a missing predictor score.
- Conservation: phyloP -0.931, GERP -1.43 — not a conserved position (phyloP < 0.1, ACGS BP7 cut)
- Molecular consequence: **frameshift** — a predicted loss-of-function variant. Gene population constraint: LOEUF 1.273, pLI 9.5209e-12. *Descriptive; not an applied PVS1 code.*
- Nonsense-mediated decay: the premature termination codon is **in exon 3 of 10**, so the transcript is predicted to undergo NMD.
- CADD: **PHRED 21.9**. No single ClinGen-calibrated threshold exists and the expert panels that use CADD disagree — GUCY2D/AIPL1 require ≥ 20.0 for an untranslated-region variant, ABCA4 ≥ 28.1 for a synonymous or indel variant, the Pulmonary Hypertension panel imports Pejaver 2022's missense-calibrated numbers, and the Antibody Deficiencies panel declines CADD entirely for PIK3CD. CADD v1.7 also incorporates Zoonomia phyloP, so it partly re-expresses the conservation above. *Descriptive; no threshold applied.*
- SpliceAI: **not assessed** — the release is built from a substitutions-only source, so it holds no deletion variants. That is a property of the dataset, not of the variant, and is not evidence against a splicing effect.
- Population frequency (gnomAD v4.1): grpmax **0.00329%** (sas) · FAF95 0.000875% · FAF99 0.000443% · 3/91,082 in the highest group · 3/1,613,390 alleles overall — very rare (popmax 0.00329%, sas).

*Computational predictors are not independent (ClinGen Variant Classification guidance): AlphaMissense (Cheng et al. 2023) carries the ACMG weight for missense and conservation (phyloP/GERP/phastCons) for non-missense; REVEL (Pejaver-2022 calibrated strength bands) and SaProt (Su et al. 2023, structure-aware, ClinVar-independent protein language model, raw LLR) are shown as orthogonal agreement signals, not additive. For frequency, the gnomAD v4.1 grpmax filtering allele frequency (FAF95) is ClinGen's designated BA1/BS1 input (gnomAD v4 guidance v3.0, June 2025); BA1/BS1 thresholds are disease-specific, not a blanket 5%. Predictions, not a clinical determination.*

## Gene constraint & dosage {#gene-context}

**SGCA** population constraint: LOEUF 1.273, pLI 9.5209e-12, missense-Z 0.64856. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

Curated gene–disease validity (ClinGen):

- **autosomal recessive limb-girdle muscular dystrophy** — Definitive (AR)

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 80.15, 47% of residues very-high.

## What this gene does {#gene-function}

*Describes the biological roles of SGCA (the gene this variant disrupts) — not effects measured for this specific variant. A damaging variant is expected to affect these functions and pathways; the degree depends on the variant.*


### Pathways affected {#pathways}

SGCA participates in **1 Reactome pathway** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| [Formation of the dystrophin-glycoprotein complex (DGC)](https://reactome.org/content/detail/R-HSA-9913351) | electronic |

## Clinical significance {#significance}

**Likely pathogenic** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2022-02-15.

**Submitter consensus:** unanimous (1/1 Likely pathogenic).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Myriad Genetics, Inc. | Likely pathogenic | criteria provided, single submitter | clinical testing | 2022-02-15 |

## Associated conditions {#conditions}

[autosomal recessive limb-girdle muscular dystrophy type 2D](https://sugi.bio/atlas/disease/autosomal-recessive-limb-girdle-muscular-dystrophy-type-2d/).

**Reported phenotype names (ClinVar):** Autosomal recessive limb-girdle muscular dystrophy type 2D, DUCHENNE-LIKE AUTOSOMAL RECESSIVE MUSCULAR DYSTROPHY, TYPE 2, MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 3, ADHALINOPATHY, PRIMARY.

## Similar variants {#similar}

Related SGCA variant pages (same residue, condition, or type): [SGCA p.Pro55Leu](/variant/sgca-p-pro55leu), [SGCA p.Asp385fs](/variant/sgca-p-asp385fs), [SGCA c.586delG](/variant/sgca-c-586delg), [SGCA c.956+2_956+19del](/variant/sgca-c-956-plus-2-956-plus-19del), [SGCA p.Ala57fs](/variant/sgca-p-ala57fs), [SGCA p.Asp266fs](/variant/sgca-p-asp266fs), [SGCA p.Gly68fs](/variant/sgca-p-gly68fs), [SGCA p.Leu131fs](/variant/sgca-p-leu131fs).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-15); AlphaMissense (Cheng et al. 2023, © Google DeepMind — CC BY 4.0, built 2026-01-27); REVEL (Ioannidis et al. 2016 — ODbL, built 2026-07-13); SaProt (Su et al. 2023 — MIT, built 2026-10-14); SpliceAI (Illumina — free for non-commercial use, built 2026-10-13); CADD (Rentzsch et al. 2019, University of Washington — free for non-commercial use, built 2026-10-10); Conservation (phyloP/phastCons/GERP) (UCSC hg38 470-way mammal (Hiller Lab) + Ensembl Compara, built 2026-07-12); gnomAD Non-coding Constraint (Gnocchi) (Chen et al. 2024, Broad Institute — CC0, built 2026-10-11); gnomAD Regional Missense Constraint (Broad Institute — CC0, built 2026-10-13); Pangolin (Zeng & Li 2022 — CC BY 4.0, built 2026-10-11); Repeat regions (UCSC — RepeatMasker, TRF, segmental duplications, built 2026-10-11); ClinGen (ClinGen, built 2026-09-22); UniProt (CC BY 4.0); Reactome / GO (CC BY 4.0, built 2026-09-23); MaveDB (per-record license, built 2026-10-11); CIViC (CC0, built 2026-09-22); Orphanet (Orphanet, built 2026-06-12)

*Primary record: NCBI ClinVar (variation 1724423). Classifications reflect these databases as of the page's build date and may change. Free reference use — not medical advice; consult the primary submitters and a clinician.*