Is BMP10 p.Arg163Trp (c.487C>T) pathogenic?

BMP10 p.Arg163Trp (c.487C>T) is classified Uncertain significance in BMP10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-25). AlphaMissense: likely benign (0.3328); Ultra-rare (popmax 0.03%, amr).

How common is BMP10 p.Arg163Trp (c.487C>T) in the general population?

BMP10 p.Arg163Trp (c.487C>T) is ultra-rare (popmax 0.03%, amr) (gnomAD).

What do computational predictors say about BMP10 p.Arg163Trp (c.487C>T)?

AlphaMissense predicts likely benign (score 0.3328) — an in-silico prediction, not a clinical call.

BMP10 p.Arg163Trp

c.487C>T · rs772544660 · VCV2568523

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3328 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.03%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3328	likely benign
REVEL	0.32	indeterminate
SaProt	LLR -9.04	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 1.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 5,470 bp · p 0.72 · regional, not allelic
Overall
CADD	18.36	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 0.03% Admixed American · 18/59,928 alleles

Filtering AF 0.0194% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.016%

Overall 0.00248% 40/1,613,488 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.03%	3,329
Finnishnot grpmax-eligible	0.00313%	31,972
East Asian	0.00223%	44,858
South Asian	0.0022%	45,519
Remaining individualsnot grpmax-eligible	0.0016%	62,468
African / African-American	0.00134%	74,730
European (non-Finnish)	0.00127%	78,662

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.Arg163Trp
Coding: c.487C>T
MANE Select: NM_014482
dbSNP: rs772544660
Type: single nucleotide variant
Location: chr2:68866419 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 74.74 · 8 PDB
Residue 163: a β-strand; 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.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.Arg96Gln Uncertain significance ★ ⚠ same type
BMP10 p.Arg96Trp 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-arg163trp (accessed [today's date]).

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