Is BMP8A p.Arg302His (c.905G>A) pathogenic?

BMP8A p.Arg302His (c.905G>A) is classified Uncertain significance in BMP8A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-29). AlphaMissense: likely benign (0.0993); Ultra-rare (popmax 0.0418%, amr).

How common is BMP8A p.Arg302His (c.905G>A) in the general population?

BMP8A p.Arg302His (c.905G>A) is ultra-rare (popmax 0.0418%, amr) (gnomAD).

What do computational predictors say about BMP8A p.Arg302His (c.905G>A)?

AlphaMissense predicts likely benign (score 0.0993) — an in-silico prediction, not a clinical call.

BMP8A p.Arg302His

c.905G>A · rs370506690 · VCV2222451

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0993 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0418%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0993	likely benign
REVEL	0.386	indeterminate
SaProt	LLR -10.42	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP -1.5, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 3,377 bp · p 0.12 · regional, not allelic
Overall
CADD	27.2	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 0.0418% Admixed American · 25/59,880 alleles

Filtering AF 0.029% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0248%

Overall 0.00502% 81/1,613,176 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0418%	2,395
East Asian	0.00669%	14,941
European (non-Finnish)	0.00407%	24,577
Remaining individualsnot grpmax-eligible	0.0032%	31,219
African / African-American	0.00267%	37,428
South Asian	0.0011%	90,914

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: BMP8A
Protein: p.Arg302His
Coding: c.905G>A
MANE Select: NM_181809
dbSNP: rs370506690
Type: single nucleotide variant
Location: chr1:39522439 (GRCh38)
Gene constraint: LOEUF 1.337 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.87
Residue 302: a disulfide bond

Full BMP8A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BMP8A p.Arg302Cys Uncertain significance ★ ⚠ same residue
BMP8A p.Ala144Val Uncertain significance ★★ ⚠ same type
BMP8A p.Arg293His Benign ★★ same type
BMP8A p.Ala102Thr Uncertain significance ★ ⚠ same type
BMP8A p.Ala201Thr Uncertain significance ★ ⚠ same type
BMP8A p.Ala264Thr Uncertain significance ★ ⚠ same type
BMP8A p.Ala348Val Uncertain significance ★ ⚠ same type
BMP8A p.Ala365Val 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/bmp8a-p-arg302his (accessed [today's date]).

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