Is SGCA p.Pro205Ser (c.613C>T) pathogenic?

SGCA p.Pro205Ser (c.613C>T) is classified Pathogenic in SGCA (ClinVar, Expert panel, 1 submitter; last evaluated 2026-04-29). AlphaMissense: likely benign (0.1302); Very rare (popmax 0.0011%, sas); Associated with autosomal recessive limb-girdle muscular dystrophy.

What condition is associated with SGCA p.Pro205Ser (c.613C>T)?

SGCA p.Pro205Ser (c.613C>T) is associated with autosomal recessive limb-girdle muscular dystrophy (ClinVar).

How common is SGCA p.Pro205Ser (c.613C>T) in the general population?

SGCA p.Pro205Ser (c.613C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about SGCA p.Pro205Ser (c.613C>T)?

AlphaMissense predicts likely benign (score 0.1302) — an in-silico prediction, not a clinical call.

SGCA p.Pro205Ser

c.613C>T · VCV4849940

Pathogenic Expert panel

Classification

Pathogenic

ClinVar

Review

Expert panel ★★★☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1302 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal recessive limb-girdle muscular dystrophy

Computational evidence

Protein change
AlphaMissense	0.1302	likely benign ⚠ discordant with ClinVar
REVEL	0.815	moderately pathogenic-leaning
SaProt	LLR -8.47	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.49 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 9,393 bp · p 0.033 · regional, not allelic
Overall
CADD	27.5	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,088 alleles

Overall 6.2e-05% 1/1,613,960 alleles · very rare exomes 1/1,461,714 · genomes 0/152,246 · joint denominator

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.Pro205Ser
Coding: c.613C>T
MANE Select: NM_000023
Type: single nucleotide variant
Location: chr17:50169120 (GRCh38)
Gene constraint: LOEUF 1.273 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.15
Residue 205: a UniProt-annotated variant site (in lgmdr3)

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

Disease context

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

Similar variants

SGCA p.Pro205His Likely pathogenic ★★★ ⚠ same residue
SGCA p.Pro205Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
SGCA p.Pro205= 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

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-pro205ser (accessed [today's date]).

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