Is BMP8A p.Glu305Val (c.914A>T) pathogenic?

BMP8A p.Glu305Val (c.914A>T) is classified Uncertain significance in BMP8A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-08). AlphaMissense: ambiguous (0.5502); Very rare (popmax 0.00585%, nfe).

How common is BMP8A p.Glu305Val (c.914A>T) in the general population?

BMP8A p.Glu305Val (c.914A>T) is very rare (popmax 0.00585%, nfe) (gnomAD).

What do computational predictors say about BMP8A p.Glu305Val (c.914A>T)?

AlphaMissense predicts ambiguous (score 0.5502) — an in-silico prediction, not a clinical call.

BMP8A p.Glu305Val

c.914A>T · VCV3481181

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5502 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00585%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5502	ambiguous
REVEL	0.911	moderately pathogenic-leaning
SaProt	LLR -12.74	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 0.77, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 3,377 bp · p 0.12 · regional, not allelic
Overall
CADD	27.1	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 0.00585% European (non-Finnish) · 69/1,179,756 alleles

Filtering AF 0.0047% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00431%

Overall 0.0044% 71/1,613,412 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00585%	17,098
Remaining individualsnot grpmax-eligible	0.0016%	62,452
African / African-American	0.00134%	74,870

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.Glu305Val
Coding: c.914A>T
MANE Select: NM_181809
Type: single nucleotide variant
Location: chr1:39522448 (GRCh38)
Gene constraint: LOEUF 1.337 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.87
Residue 305: a disulfide bond

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

Similar variants

BMP8A p.Glu305Lys 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-glu305val (accessed [today's date]).

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