Is BMP8B p.Ala365Val (c.1094C>T) pathogenic?

BMP8B p.Ala365Val (c.1094C>T) is classified Uncertain significance in BMP8B (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-13). AlphaMissense: ambiguous (0.3975); Rare (popmax 0.112%, afr).

How common is BMP8B p.Ala365Val (c.1094C>T) in the general population?

BMP8B p.Ala365Val (c.1094C>T) is rare (popmax 0.112%, afr) (gnomAD).

What do computational predictors say about BMP8B p.Ala365Val (c.1094C>T)?

AlphaMissense predicts ambiguous (score 0.3975) — an in-silico prediction, not a clinical call.

BMP8B p.Ala365Val

c.1094C>T · rs147897246 · VCV2216896

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3975 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.112%, afr)

Computational evidence

Protein change
AlphaMissense	0.3975	ambiguous
REVEL	0.343	indeterminate
SaProt	LLR -8.88	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 0.87, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 3,342 bp · p 0.027 · regional, not allelic
Overall
CADD	17.05	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 0.112% African / African-American · 84/74,904 alleles

Filtering AF 0.0928% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0856%

Overall 0.0103% 167/1,613,906 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.112%	892
Remaining individualsnot grpmax-eligible	0.0224%	4,463
Admixed American	0.0167%	6,001
Middle Eastern	0.0165%	6,058
South Asian	0.00659%	15,181
European (non-Finnish)	0.00432%	23,137
Finnishnot grpmax-eligible	0.00156%	63,970

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: BMP8B
Protein: p.Ala365Val
Coding: c.1094C>T
MANE Select: NM_001720
dbSNP: rs147897246
Type: single nucleotide variant
Location: chr1:39760534 (GRCh38)
Gene constraint: LOEUF 1.297 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.96
Residue 365: a disulfide bond

Full BMP8B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BMP8B p.Ala365= Likely benign ★ same residue
BMP8B c.1059+579A>G Benign/Likely benign ★★ same type
BMP8B p.Leu118= Likely benign ★★ same type
BMP8B p.Ser276Thr Benign ★★ same type
BMP8B p.Ser326= Benign/Likely benign ★★ same type
BMP8B c.673+3659A>G Conflicting classifications of pathogenicity ★ ⚠ same type
BMP8B p.Ala344Val Uncertain significance ★ ⚠ same type
BMP8B p.Ala348Thr 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/bmp8b-p-ala365val (accessed [today's date]).

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