Is BMP10 p.Glu87Lys (c.259G>A) pathogenic?

BMP10 p.Glu87Lys (c.259G>A) is classified Uncertain significance in BMP10 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-13). AlphaMissense: likely pathogenic (0.6833); Very rare (popmax 0.0022%, sas).

How common is BMP10 p.Glu87Lys (c.259G>A) in the general population?

BMP10 p.Glu87Lys (c.259G>A) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about BMP10 p.Glu87Lys (c.259G>A)?

AlphaMissense predicts likely pathogenic (score 0.6833) — an in-silico prediction, not a clinical call.

BMP10 p.Glu87Lys

c.259G>A · rs756550591 · VCV2536814

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6833 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6833	likely pathogenic
REVEL	0.401	indeterminate
SaProt	LLR -6.65	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 5,470 bp · p 0.72 · regional, not allelic
Overall
CADD	26.2	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 0.0022% South Asian · 2/91,084 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000205% 3/1,461,814 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,542
Remaining individualsnot grpmax-eligible	0.0016%	62,506

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.Glu87Lys
Coding: c.259G>A
MANE Select: NM_014482
dbSNP: rs756550591
Type: single nucleotide variant
Location: chr2:68871100 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 74.74 · 8 PDB
Residue 87: an α-helix; 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.Arg163Trp Uncertain significance ★ ⚠ same type
BMP10 p.Arg96Gln Uncertain significance ★ ⚠ same type
BMP10 p.Arg96Trp 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-glu87lys (accessed [today's date]).

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