Is BMP8A p.Val44Met (c.130G>A) pathogenic?

BMP8A p.Val44Met (c.130G>A) is classified Likely benign in BMP8A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-22). AlphaMissense: likely benign (0.0965); Ultra-rare (popmax 0.0651%, mid).

How common is BMP8A p.Val44Met (c.130G>A) in the general population?

BMP8A p.Val44Met (c.130G>A) is ultra-rare (popmax 0.0651%, mid) (gnomAD).

What do computational predictors say about BMP8A p.Val44Met (c.130G>A)?

AlphaMissense predicts likely benign (score 0.0965) — an in-silico prediction, not a clinical call.

BMP8A p.Val44Met

c.130G>A · VCV4646237

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0965 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0651%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0965	likely benign
REVEL	0.1	moderately benign-leaning
SaProt	LLR -7.00	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -2.4, phastCons 0.99
Regional constraint	o/e 0.76	unconstrained · MANE · 167 bp · p 0.035 · regional, not allelic
Overall
CADD	11.77	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 0.0651% Middle Eastern · 2/3,072 alleles

Filtering AF 0.0115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00475%

Overall 0.00107% 13/1,216,026 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0651%	1,536
Admixed American	0.00885%	11,294
Remaining individualsnot grpmax-eligible	0.00231%	43,380
African / African-American	0.0016%	62,542
European (non-Finnish)	0.000714%	140,005

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.Val44Met
Coding: c.130G>A
MANE Select: NM_181809
Type: single nucleotide variant
Location: chr1:39492121 (GRCh38)
Gene constraint: LOEUF 1.337 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.87

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

Similar variants

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
BMP8A p.Ala374Thr 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-val44met (accessed [today's date]).

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