Is SGCA p.Ser377= (c.1131C>T) pathogenic?

SGCA p.Ser377= (c.1131C>T) is classified Likely benign in SGCA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-08-16). Ultra-rare (popmax 0.0494%, mid); Associated with autosomal recessive limb-girdle muscular dystrophy type 2D.

What condition is associated with SGCA p.Ser377= (c.1131C>T)?

SGCA p.Ser377= (c.1131C>T) is associated with autosomal recessive limb-girdle muscular dystrophy type 2D (ClinVar).

How common is SGCA p.Ser377= (c.1131C>T) in the general population?

SGCA p.Ser377= (c.1131C>T) is ultra-rare (popmax 0.0494%, mid) (gnomAD).

SGCA p.Ser377=

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.1131C>T · rs769951787 · VCV1081880

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0494%, mid)

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2D

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.074	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP -3.4	GERP -3
Overall
CADD	12.03	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0494% Middle Eastern · 3/6,072 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00717%

Overall 0.00105% 17/1,613,040 alleles · ultra-rare exomes 15/1,460,780 · genomes 2/152,260 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0494%	2,024
Remaining individualsnot grpmax-eligible	0.0032%	31,236
Finnishnot grpmax-eligible	0.00317%	31,516
Admixed American	0.00167%	60,004
South Asian	0.0011%	91,066
European (non-Finnish)	0.000678%	147,505

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: SGCA
Protein: p.Ser377=
Coding: c.1131C>T
MANE Select: NM_000023
dbSNP: rs769951787
Type: single nucleotide variant
Location: chr17:50175404 (GRCh38)
Gene constraint: LOEUF 1.273 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.15
Residue 377: a modified residue (phosphoserine)

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.Ser377Gly Uncertain significance ★ ⚠ 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-ser377 (accessed [today's date]).

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