Is BMP10 p.Ser275Ala (c.823T>G) pathogenic?

BMP10 p.Ser275Ala (c.823T>G) is classified Likely benign in BMP10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-13). AlphaMissense: likely benign (0.0657); Very rare (popmax 0.00636%, nfe).

How common is BMP10 p.Ser275Ala (c.823T>G) in the general population?

BMP10 p.Ser275Ala (c.823T>G) is very rare (popmax 0.00636%, nfe) (gnomAD).

What do computational predictors say about BMP10 p.Ser275Ala (c.823T>G)?

AlphaMissense predicts likely benign (score 0.0657) — an in-silico prediction, not a clinical call.

BMP10 p.Ser275Ala

c.823T>G · VCV4214243

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0657 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00636%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0657	likely benign
REVEL	0.066	moderately benign-leaning
SaProt	LLR -5.62	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	GERP -5.6
Regional constraint	o/e 0.98	unconstrained · MANE · 5,470 bp · p 0.72 · regional, not allelic
Overall
CADD	0.576	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 0.00636% European (non-Finnish) · 75/1,179,992 alleles

Filtering AF 0.00519% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00474%

Overall 0.00477% 77/1,613,940 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00636%	15,733
African / African-American	0.00267%	37,456

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.Ser275Ala
Coding: c.823T>G
MANE Select: NM_014482
Type: single nucleotide variant
Location: chr2:68866083 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 74.74 · 8 PDB
Residue 275: 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-ser275ala (accessed [today's date]).

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