Is BMP8A p.Arg147Gln (c.440G>A) pathogenic?

BMP8A p.Arg147Gln (c.440G>A) is classified Uncertain significance in BMP8A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-20). AlphaMissense: likely benign (0.2958); Ultra-rare (popmax 0.0282%, mid).

How common is BMP8A p.Arg147Gln (c.440G>A) in the general population?

BMP8A p.Arg147Gln (c.440G>A) is ultra-rare (popmax 0.0282%, mid) (gnomAD).

What do computational predictors say about BMP8A p.Arg147Gln (c.440G>A)?

AlphaMissense predicts likely benign (score 0.2958) — an in-silico prediction, not a clinical call.

BMP8A p.Arg147Gln

c.440G>A · VCV3481187

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2958 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0282%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2958	likely benign
REVEL	0.726	pathogenic-leaning
SaProt	LLR -8.97	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 0.82, phastCons 1
Regional constraint	o/e 0.17	constrained · MANE · 165 bp · p 5.5e-13 · regional, not allelic
Overall
CADD	28.1	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 0.0282% Middle Eastern · 1/3,550 alleles

Filtering AF 0.0087% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00666%

Overall 0.00532% 65/1,221,556 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0282%	3,550
South Asian	0.0155%	6,443
Ashkenazi Jewishnot grpmax-eligible	0.0124%	8,046
Remaining individualsnot grpmax-eligible	0.0103%	9,700
African / African-American	0.00475%	21,033
European (non-Finnish)	0.00472%	21,174
East Asian	0.00256%	39,058

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.Arg147Gln
Coding: c.440G>A
MANE Select: NM_181809
Type: single nucleotide variant
Location: chr1:39511279 (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-arg147gln (accessed [today's date]).

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