Is BSG p.Val337Ala (c.1010T>C) pathogenic?

BSG p.Val337Ala (c.1010T>C) is classified Uncertain significance in BSG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). AlphaMissense: likely pathogenic (0.7948); Absent from gnomAD v4.1.

How common is BSG p.Val337Ala (c.1010T>C) in the general population?

BSG p.Val337Ala (c.1010T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BSG p.Val337Ala (c.1010T>C)?

AlphaMissense predicts likely pathogenic (score 0.7948) — an in-silico prediction, not a clinical call.

BSG p.Val337Ala

c.1010T>C · VCV4216454

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7948 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7948	likely pathogenic
REVEL	0.296	indeterminate
SaProt	LLR -11.34	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 0.21, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 9,939 bp · p 0.057 · regional, not allelic
Overall
CADD	28.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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: BSG
Protein: p.Val337Ala
Coding: c.1010T>C
MANE Select: NM_001728
Type: single nucleotide variant
Location: chr19:581532 (GRCh38)
Gene constraint: LOEUF 1.254 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.51 · 18 PDB
Residue 337: an α-helix

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

Similar variants

BSG c.*238C>T Benign ★★ same type
BSG p.Ser283= Benign ★★ same type
BSG p.Ala163Thr Uncertain significance ★ ⚠ same type
BSG p.Ala225Pro Uncertain significance ★ ⚠ same type
BSG p.Ala360Thr Uncertain significance ★ ⚠ same type
BSG p.Ala4Gly Uncertain significance ★ ⚠ same type
BSG p.Ala4Thr Uncertain significance ★ ⚠ same type
BSG p.Arg282Gln Uncertain significance ★ ⚠ same type

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/bsg-p-val337ala (accessed [today's date]).

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