Is SGCA p.Met1Val (c.1A>G) pathogenic?

SGCA p.Met1Val (c.1A>G) is classified Pathogenic/Likely pathogenic in SGCA (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-07-10). Very rare (popmax 0.00017%, nfe); Associated with autosomal recessive limb-girdle muscular dystrophy.

What condition is associated with SGCA p.Met1Val (c.1A>G)?

SGCA p.Met1Val (c.1A>G) is associated with autosomal recessive limb-girdle muscular dystrophy, autosomal recessive limb-girdle muscular dystrophy type 2D (ClinVar).

How common is SGCA p.Met1Val (c.1A>G) in the general population?

SGCA p.Met1Val (c.1A>G) is very rare (popmax 0.00017%, nfe) (gnomAD).

SGCA p.Met1Val

c.1A>G · rs2509113878 · VCV1705242

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

start-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

autosomal recessive limb-girdle muscular dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function
REVEL	0.697	pathogenic-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1, phastCons 1
Overall
CADD	22.3	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,516 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,394 alleles · very rare exomes 2/1,461,246 · genomes 0/152,148 · 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.Met1Val
Coding: c.1A>G
MANE Select: NM_000023
dbSNP: rs2509113878
Type: single nucleotide variant
Location: chr17:50166041 (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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive limb-girdle muscular dystrophy type 2D

Similar variants

SGCA p.Met1fs Likely pathogenic 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-met1val (accessed [today's date]).

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