Is BMS1 p.Arg930His (c.2789G>A) pathogenic?

BMS1 p.Arg930His (c.2789G>A) is classified Pathogenic in BMS1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2013-06-01). AlphaMissense: likely pathogenic (0.9258); Very rare (popmax 0.00268%, afr); Associated with aplasia cutis congenita.

What condition is associated with BMS1 p.Arg930His (c.2789G>A)?

BMS1 p.Arg930His (c.2789G>A) is associated with aplasia cutis congenita (ClinVar).

How common is BMS1 p.Arg930His (c.2789G>A) in the general population?

BMS1 p.Arg930His (c.2789G>A) is very rare (popmax 0.00268%, afr) (gnomAD).

What do computational predictors say about BMS1 p.Arg930His (c.2789G>A)?

AlphaMissense predicts likely pathogenic (score 0.9258) — an in-silico prediction, not a clinical call.

BMS1 p.Arg930His

c.2789G>A · rs587777706 · VCV155924

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9258 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00268%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

aplasia cutis congenita

Computational evidence

Protein change
AlphaMissense	0.9258	likely pathogenic ✓ concordant with ClinVar
REVEL	0.509	indeterminate
SaProt	LLR -11.72	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 9.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 14 kb · p 1.9e-09 · regional, not allelic
Overall
CADD	32.0	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 0.00268% African / African-American · 2/74,644 alleles

Filtering AF 0.000543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000429%

Overall 0.000994% 16/1,610,010 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00268%	37,322
East Asian	0.00223%	44,878
South Asian	0.0011%	90,648
European (non-Finnish)	0.00102%	98,271

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.Arg930His
Coding: c.2789G>A
MANE Select: NM_014753
dbSNP: rs587777706
Type: single nucleotide variant
Location: chr10:42820527 (GRCh38)
Gene constraint: LOEUF 0.507 · pLI 0.50 (gnomAD)
Structure: AlphaFold pLDDT 72.04 · 3 PDB
Residue 930: a UniProt-annotated variant site (in acc; fibroblasts show cdkn1a-mediated g1/s phase transition defect with a significantly reduced cell proliferation rate compared to controls; in vitro scratch assay reveal an increased cell migration rate)

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

Disease context

aplasia cutis congenita — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BMS1 p.Leu732Val Uncertain significance ★ ⚠ same condition
BMS1 p.Pro742Leu Uncertain significance ★ ⚠ same condition
BMS1 p.Ser295fs Uncertain significance ★ same condition
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

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-arg930his (accessed [today's date]).

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