Is BMS1 p.Ala214Val (c.641C>T) pathogenic?

BMS1 p.Ala214Val (c.641C>T) is classified Benign/Likely benign in BMS1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-11-13). AlphaMissense: likely pathogenic (0.9761); Rare (popmax 0.616%, eas).

How common is BMS1 p.Ala214Val (c.641C>T) in the general population?

BMS1 p.Ala214Val (c.641C>T) is rare (popmax 0.616%, eas) (gnomAD).

What do computational predictors say about BMS1 p.Ala214Val (c.641C>T)?

AlphaMissense predicts likely pathogenic (score 0.9761) — an in-silico prediction, not a clinical call.

BMS1 p.Ala214Val

c.641C>T · rs141772670 · VCV734056

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9761 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.616%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9761	likely pathogenic · top 8% in BMS1
REVEL	0.367	indeterminate
SaProt	LLR -14.29	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 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 7,350 bp · p 3.4e-05 · regional, not allelic
Overall
CADD	26.8	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 0.616% East Asian · 272/44,122 alleles

Filtering AF 0.556% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.533%

Overall 0.0808% 1,290/1,596,964 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.616%	162
Admixed American	0.378%	264
South Asian	0.296%	338
African / African-American	0.256%	390
Remaining individualsnot grpmax-eligible	0.165%	605
Middle Eastern	0.0702%	1,424
European (non-Finnish)	0.0215%	4,644
Ashkenazi Jewishnot grpmax-eligible	0.00344%	29,034

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.Ala214Val
Coding: c.641C>T
MANE Select: NM_014753
dbSNP: rs141772670
Type: single nucleotide variant
Location: chr10:42791631 (GRCh38)
Gene constraint: LOEUF 0.507 · pLI 0.50 (gnomAD)
Structure: AlphaFold pLDDT 72.04 · 3 PDB
Residue 214: the bms1-type g domain

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

Similar variants

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
BMS1 p.Leu257= 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-ala214val (accessed [today's date]).

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