Is SGCA p.Pro130Ser (c.388C>T) pathogenic?

SGCA p.Pro130Ser (c.388C>T) is classified Uncertain significance in SGCA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-31). AlphaMissense: likely benign (0.0881); No allele count reported in gnomAD v4.1 (AN 1,571,452); Associated with autosomal recessive limb-girdle muscular dystrophy type 2D.

What condition is associated with SGCA p.Pro130Ser (c.388C>T)?

SGCA p.Pro130Ser (c.388C>T) is associated with autosomal recessive limb-girdle muscular dystrophy type 2D (ClinVar).

How common is SGCA p.Pro130Ser (c.388C>T) in the general population?

SGCA p.Pro130Ser (c.388C>T) is no allele count reported in gnomAD v4.1 (AN 1,571,452) (gnomAD).

What do computational predictors say about SGCA p.Pro130Ser (c.388C>T)?

AlphaMissense predicts likely benign (score 0.0881) — an in-silico prediction, not a clinical call.

SGCA p.Pro130Ser

Q: How is Alpha-sarcoglycan-related limb-girdle muscular dystrophy R3 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.388C>T · rs2509121515 · VCV1941662

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0881 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,571,452)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2D

Computational evidence

Protein change
AlphaMissense	0.0881	likely benign
REVEL	0.316	indeterminate
SaProt	LLR -9.30	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.8	GERP 1.4, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 9,393 bp · p 0.033 · regional, not allelic
Overall
CADD	16.39	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,571,452). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SGCA
Protein: p.Pro130Ser
Coding: c.388C>T
MANE Select: NM_000023
dbSNP: rs2509121515
Type: single nucleotide variant
Location: chr17:50168376 (GRCh38)
Gene constraint: LOEUF 1.273 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.15

Full SGCA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive limb-girdle muscular dystrophy type 2D — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Alpha-sarcoglycan-related limb-girdle muscular dystrophy R3 (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Childhood
Prevalence: <1 / 1 000 000 (United Kingdom)

Similar variants

SGCA p.Pro130= Likely benign ★ same residue
SGCA c.37+6T>C Pathogenic ★★★ same condition
SGCA c.585-1G>A Pathogenic ★★★ same condition
SGCA c.957-11C>G Likely pathogenic ★★★ same condition
SGCA p.Ala107Val Likely pathogenic ★★★ ⚠ same condition
SGCA p.Arg192Ter Pathogenic ★★★ same condition
SGCA p.Arg221Cys Likely pathogenic ★★★ same condition
SGCA p.Arg221Pro Likely pathogenic ★★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/sgca-p-pro130ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown