Is BMP8A p.Arg293His (c.878G>A) pathogenic?

BMP8A p.Arg293His (c.878G>A) is classified Benign in BMP8A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2017-06-06). AlphaMissense: likely benign (0.0555); Common (popmax 70%, sas) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about BMP8A p.Arg293His (c.878G>A)?

AlphaMissense predicts likely benign (score 0.0555) — an in-silico prediction, not a clinical call.

BMP8A p.Arg293His

Q: How common is BMP8A p.Arg293His (c.878G>A) in the general population?

BMP8A p.Arg293His (c.878G>A) is common (popmax 70%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.878G>A · rs6525 · VCV767666

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0555 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 70%, sas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0555	likely benign
REVEL	0.088	moderately benign-leaning
SaProt	LLR -5.76	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 2.4	GERP -3.5, phastCons 0.84
Regional constraint	o/e 0.21	constrained · MANE · 909 bp · p 3.3e-05 · regional, not allelic
Overall
CADD	6.072	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 70% South Asian · 55,375/79,074 alleles

Filtering AF 69.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 69.3%

Overall 50.7% 658,968/1,299,952 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	70%	1
Amishnot grpmax-eligible	67.9%	1
East Asian	51.5%	2
Remaining individualsnot grpmax-eligible	51.2%	2
European (non-Finnish)	51.1%	2
Ashkenazi Jewishnot grpmax-eligible	50.7%	2
Admixed American	50.1%	2
Finnishnot grpmax-eligible	46.9%	2
Middle Eastern	45.8%	2
African / African-American	24.5%	4

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.Arg293His
Coding: c.878G>A
MANE Select: NM_181809
dbSNP: rs6525
Type: single nucleotide variant
Location: chr1:39522412 (GRCh38)
Gene constraint: LOEUF 1.337 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.87
Residue 293: a UniProt-annotated variant site (in)

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.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
BMP8A p.Ala38Pro 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-arg293his (accessed [today's date]).

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