Is BSG p.Ile232Val (c.694A>G) pathogenic?

BSG p.Ile232Val (c.694A>G) is classified Likely benign in BSG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-04). AlphaMissense: likely benign (0.0763); Ultra-rare (popmax 0.0112%, nfe).

How common is BSG p.Ile232Val (c.694A>G) in the general population?

BSG p.Ile232Val (c.694A>G) is ultra-rare (popmax 0.0112%, nfe) (gnomAD).

What do computational predictors say about BSG p.Ile232Val (c.694A>G)?

AlphaMissense predicts likely benign (score 0.0763) — an in-silico prediction, not a clinical call.

BSG p.Ile232Val

c.694A>G · VCV4216449

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0763 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0112%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0763	likely benign
REVEL	0.078	moderately benign-leaning
SaProt	LLR -5.40	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -2.4, phastCons 0.009
Regional constraint	o/e 1.08	unconstrained · MANE · 9,939 bp · p 0.057 · regional, not allelic
Overall
CADD	3.577	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 0.0112% European (non-Finnish) · 132/1,179,982 alleles

Filtering AF 0.00961% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00904%

Overall 0.00862% 139/1,612,754 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0112%	8,939
Admixed American	0.00833%	12,002
Remaining individualsnot grpmax-eligible	0.0016%	62,468
African / African-American	0.00133%	74,920

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: BSG
Protein: p.Ile232Val
Coding: c.694A>G
MANE Select: NM_001728
Type: single nucleotide variant
Location: chr19:580684 (GRCh38)
Gene constraint: LOEUF 1.254 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.51 · 18 PDB
Residue 232: a β-strand; the ig-like v-type domain

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-ile232val (accessed [today's date]).

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