Is BMS1 p.Val84Ala (c.251T>C) pathogenic?

BMS1 p.Val84Ala (c.251T>C) is classified Uncertain significance in BMS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-05). AlphaMissense: ambiguous (0.3881); Ultra-rare (popmax 0.0178%, eas).

How common is BMS1 p.Val84Ala (c.251T>C) in the general population?

BMS1 p.Val84Ala (c.251T>C) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

What do computational predictors say about BMS1 p.Val84Ala (c.251T>C)?

AlphaMissense predicts ambiguous (score 0.3881) — an in-silico prediction, not a clinical call.

BMS1 p.Val84Ala

c.251T>C · rs1554792420 · VCV2332523

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3881 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Computational evidence

Protein change
AlphaMissense	0.3881	ambiguous
REVEL	0.316	indeterminate
SaProt	LLR -11.61	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 7,350 bp · p 3.4e-05 · regional, not allelic
Overall
CADD	24.6	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 0.0178% East Asian · 8/44,890 alleles

Filtering AF 0.00883% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.000558% 9/1,613,748 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,611
Remaining individualsnot grpmax-eligible	0.0016%	62,468

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: BMS1
Protein: p.Val84Ala
Coding: c.251T>C
MANE Select: NM_014753
dbSNP: rs1554792420
Type: single nucleotide variant
Location: chr10:42785556 (GRCh38)
Gene constraint: LOEUF 0.507 · pLI 0.50 (gnomAD)
Structure: AlphaFold pLDDT 72.04 · 3 PDB
Residue 84: the bms1-type g domain; a β-strand

Full BMS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BMS1 p.Ala214Val Benign/Likely benign ★★ same type
BMS1 p.Ala500= Benign/Likely benign ★★ same type
BMS1 p.Arg237His Benign ★★ same type
BMS1 p.Arg38Trp Benign/Likely benign ★★ ⚠ same type
BMS1 p.Arg863= Benign ★★ same type
BMS1 p.Asp768Asn Benign ★★ same type
BMS1 p.Glu1278= Likely benign ★★ same type
BMS1 p.Ile942= Benign/Likely benign ★★ 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/bms1-p-val84ala (accessed [today's date]).

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