Is BMP10 p.Arg96Gln (c.287G>A) pathogenic?

BMP10 p.Arg96Gln (c.287G>A) is classified Uncertain significance in BMP10 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-31). AlphaMissense: likely benign (0.0921); Ultra-rare (popmax 0.0156%, eas).

How common is BMP10 p.Arg96Gln (c.287G>A) in the general population?

BMP10 p.Arg96Gln (c.287G>A) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

What do computational predictors say about BMP10 p.Arg96Gln (c.287G>A)?

AlphaMissense predicts likely benign (score 0.0921) — an in-silico prediction, not a clinical call.

BMP10 p.Arg96Gln

c.287G>A · rs377683224 · VCV3134506

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0921 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0921	likely benign
REVEL	0.184	benign-leaning
SaProt	LLR -5.48	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 6	GERP 0.97, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 5,470 bp · p 0.72 · regional, not allelic
Overall
CADD	28.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0156% East Asian · 7/44,902 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00514%

Overall 0.00204% 33/1,613,856 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,415
Remaining individualsnot grpmax-eligible	0.0144%	6,942
African / African-American	0.0107%	9,361
South Asian	0.0022%	45,534
Finnishnot grpmax-eligible	0.00156%	63,916
European (non-Finnish)	0.000508%	196,668

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: BMP10
Protein: p.Arg96Gln
Coding: c.287G>A
MANE Select: NM_014482
dbSNP: rs377683224
Type: single nucleotide variant
Location: chr2:68871072 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 74.74 · 8 PDB
Residue 96: a UniProt-annotated variant site (found in a family with congenital heart defects; likely pathogenic; loss of function in bmp signaling pathway; contrary to the wild type, it is unable to stimulate gene expression from tbx20 and nkx2-5 promoters in a luciferase reporter assay)

Full BMP10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BMP10 p.Arg96Trp Uncertain significance ★ ⚠ same residue
BMP10 p.Asn250Lys Benign ★★ same type
BMP10 p.Thr200Ser Benign/Likely benign ★★ same type
BMP10 p.Ala298Thr Uncertain significance ★ ⚠ same type
BMP10 p.Arg155Cys Uncertain significance ★ ⚠ same type
BMP10 p.Arg155His Uncertain significance ★ ⚠ same type
BMP10 p.Arg163Trp Uncertain significance ★ ⚠ same type
BMP10 p.Asn90Asp 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/bmp10-p-arg96gln (accessed [today's date]).

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