# NM_004415.4(DSP):c.153G>A (p.Gln51=)

https://sugi.bio/variant/dsp-p-gln51

## Summary

**DSP p.Gln51= (c.153G>A)** is classified **Likely benign** in DSP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-10-09). Very rare (popmax 0.000519%, nfe); Associated with arrhythmogenic cardiomyopathy with wooly hair and keratoderma.

**At a glance:** Likely benign · review: Multiple submitters · rsID rs1450725914 · 2 submitters · 2 linked conditions · very rare (popmax 0.000519%, nfe)

## For patients & families {#patients}

This is a change in the DSP gene that is classified as likely benign — not considered disease-causing, submitted by 2 submitters, and is linked to arrhythmogenic cardiomyopathy with wooly hair and keratoderma.

*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 dominant, Autosomal recessive |
| Age of onset (of this condition) | Childhood, Infancy, Neonatal |

**Commonly reported features of Carvajal syndrome** (across patients with this condition; presentation varies — frequencies from Orphanet):

- Dilated cardiomyopathy — Very frequent (99-80%)
- Woolly hair — Very frequent (99-80%)
- Patchy palmoplantar keratoderma — Very frequent (99-80%)
- Congestive heart failure — Occasional (29-5%)

**Support & next steps:** [Condition overview & support (NIH GARD)](https://rarediseases.info.nih.gov/diseases/0005595/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [DSP](https://sugi.bio/atlas/gene/DSP/) |
| Protein change (HGVS p.) | p.Gln51= |
| Coding change (HGVS c.) | c.153G>A |
| dbSNP | [rs1450725914](https://www.ncbi.nlm.nih.gov/snp/rs1450725914/) |
| Variant type | single nucleotide variant |
| Location | chr6:7542068-7542068 (GRCh38) |
| ClinVar | [VCV1082213](https://www.ncbi.nlm.nih.gov/clinvar/variation/1082213/) |

**All HGVS expressions:** `LRG_423:g.5432G>A`, `LRG_423t1:c.153G>A`, `NC_000006.11:g.7542301G>A`, `NC_000006.12:g.7542068G>A`, `NG_008803.1:g.5432G>A`, `NM_001008844.3:c.153G>A`, `NM_001319034.2:c.153G>A`, `NM_004415.4:c.153G>A`

## 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 2.726, GERP -1.09, phastCons 1 — highly conserved position (PP3-type support)
- CADD: **PHRED 9.826**. 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 looked up on this page** — it was served without the gene's SpliceAI index, so no lookup was made. This is a gap in this page, not in the data, and says nothing about whether a splicing effect is predicted.
- Population frequency (gnomAD v4.1): grpmax **0.000519%** (nfe) · FAF95 0.000187% · FAF99 0.000123% · 6/1,155,142 in the highest group · 6/1,565,020 alleles overall — very rare (popmax 0.000519%, nfe).

*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.*

## Clinical significance {#significance}

**Likely benign** — review status Multiple submitters *(criteria provided, multiple submitters, no conflicts)*, last evaluated 2022-10-09.

**Submitter consensus:** unanimous (2/2 Likely benign).

**Submission history:** 2 submissions (2020–2022); classifications have been stable.

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Ambry Genetics | Likely benign | criteria provided, single submitter | clinical testing | 2020-03-17 |
| Labcorp Genetics (formerly Invitae), Labcorp | Likely benign | criteria provided, single submitter | clinical testing | 2022-10-09 |

## Associated conditions {#conditions}

[arrhythmogenic cardiomyopathy with wooly hair and keratoderma](https://sugi.bio/atlas/disease/arrhythmogenic-cardiomyopathy-with-wooly-hair-and-keratoderma/), [arrhythmogenic right ventricular dysplasia 8](https://sugi.bio/atlas/disease/arrhythmogenic-right-ventricular-dysplasia-8/).

**Reported phenotype names (ClinVar):** Arrhythmogenic cardiomyopathy with wooly hair and keratoderma, Arrhythmogenic right ventricular dysplasia 8, Cardiovascular phenotype, Carvajal syndrome, Dilated cardiomyopathy with woolly hair and keratoderma, Arrhythmogenic cardiomyopathy with woolly hair and keratoderma, PALMOPLANTAR KERATODERMA WITH LEFT VENTRICULAR CARDIOMYOPATHY AND WOOLLY HAIR, Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy 8, ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY 8, ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA, FAMILIAL, 8.

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-11); gnomAD v4.1 (Broad Institute, built 2026-10-06); 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 2026-07-14); 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 1082213). 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.*