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

BVES p.Met1Val (c.1A>G) is classified Pathogenic in BVES (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-08-25). Very rare (popmax 0.00197%, amr); Associated with autosomal recessive limb-girdle muscular dystrophy type 2X.

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

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

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

BVES p.Met1Val (c.1A>G) is very rare (popmax 0.00197%, amr) (gnomAD).

How is BVES-related limb-girdle muscular dystrophy inherited?

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

BVES p.Met1Val

c.1A>G · rs1332603843 · VCV626315

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

start-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00197%, amr)

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2X

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	0.269	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.3, phastCons 1
Overall
CADD	21.9	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 0.00197% Admixed American · 1/50,706 alleles

Filtering AF 8.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.5e-05%

Overall 0.000319% 5/1,568,556 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00197%	50,706
European (non-Finnish)	0.000345%	289,533

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: BVES
Protein: p.Met1Val
Coding: c.1A>G
MANE Select: NM_001199563
dbSNP: rs1332603843
Type: single nucleotide variant
Location: chr6:105133577 (GRCh38)
Gene constraint: LOEUF 0.915 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.08

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

Disease context

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

For BVES-related limb-girdle muscular dystrophy (Orphanet):

Inheritance: Autosomal recessive
Onset: Adult

Similar variants

POPDC1 p.Arg88Ter Pathogenic/Likely pathogenic ★★ same condition
POPDC1 p.Ser201Phe Likely pathogenic ★★ same condition
POPDC1 p.Arg129Gln Uncertain significance ★★ ⚠ same condition
POPDC1 p.Arg172His Uncertain significance ★★ ⚠ same condition
POPDC1 p.Arg311Gln Uncertain significance ★★ ⚠ same condition
POPDC1 p.Arg88Gln Uncertain significance ★★ ⚠ same condition
POPDC1 p.Asp304Asn Uncertain significance ★★ ⚠ same condition
POPDC1 p.His279Arg Uncertain significance ★★ ⚠ 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/bves-p-met1val (accessed [today's date]).

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