Is BMS1 p.Arg863Cys (c.2587C>T) pathogenic?

BMS1 p.Arg863Cys (c.2587C>T) is classified Uncertain significance in BMS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-11). AlphaMissense: likely benign (0.1491); Very rare (popmax 0.00891%, eas).

How common is BMS1 p.Arg863Cys (c.2587C>T) in the general population?

BMS1 p.Arg863Cys (c.2587C>T) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about BMS1 p.Arg863Cys (c.2587C>T)?

AlphaMissense predicts likely benign (score 0.1491) — an in-silico prediction, not a clinical call.

BMS1 p.Arg863Cys

c.2587C>T · VCV3992248

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1491 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1491	likely benign
REVEL	0.182	moderately benign-leaning
SaProt	LLR -10.96	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 0.52, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 14 kb · p 1.9e-09 · regional, not allelic
Overall
CADD	21.6	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 0.00891% East Asian · 4/44,900 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0021%

Overall 0.00273% 44/1,611,244 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,225
European (non-Finnish)	0.00322%	31,049
Remaining individualsnot grpmax-eligible	0.0016%	62,452
African / African-American	0.00134%	74,878

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.Arg863Cys
Coding: c.2587C>T
MANE Select: NM_014753
Type: single nucleotide variant
Location: chr10:42820242 (GRCh38)
Gene constraint: LOEUF 0.507 · pLI 0.50 (gnomAD)
Structure: AlphaFold pLDDT 72.04 · 3 PDB
Residue 863: an α-helix

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

Similar variants

BMS1 p.Arg863= Benign ★★ same residue
BMS1 p.Arg863His Uncertain significance ★ ⚠ same residue
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.Asp768Asn Benign ★★ same type
BMS1 p.Glu1278= 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-arg863cys (accessed [today's date]).

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