Is BVES p.Ile193Ser (c.578T>G) pathogenic?

BVES p.Ile193Ser (c.578T>G) is classified Pathogenic in BVES (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-08-25). AlphaMissense: likely pathogenic (0.9946); Absent from gnomAD v4.1; Associated with autosomal recessive limb-girdle muscular dystrophy type 2X.

What condition is associated with BVES p.Ile193Ser (c.578T>G)?

BVES p.Ile193Ser (c.578T>G) is associated with autosomal recessive limb-girdle muscular dystrophy type 2X (ClinVar).

How common is BVES p.Ile193Ser (c.578T>G) in the general population?

BVES p.Ile193Ser (c.578T>G) is absent from gnomAD v4.1 (gnomAD).

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

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

What do computational predictors say about BVES p.Ile193Ser (c.578T>G)?

AlphaMissense predicts likely pathogenic (score 0.9946) — an in-silico prediction, not a clinical call.

BVES p.Ile193Ser

c.578T>G · rs2114489353 · VCV1702994

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9946 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2X

Computational evidence

Protein change
AlphaMissense	0.9946	likely pathogenic ✓ concordant with ClinVar · top 5% in BVES
REVEL	0.814	moderately pathogenic-leaning
SaProt	LLR -13.37	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.36	acceptor loss, 21 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 11	GERP 2.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 32 kb · p 0.55 · regional, not allelic
Overall
CADD	29.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BVES
Protein: p.Ile193Ser
Coding: c.578T>G
MANE Select: NM_001199563
dbSNP: rs2114489353
Type: single nucleotide variant
Location: chr6:105124617 (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-ile193ser (accessed [today's date]).

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