Is BMP10 p.Ser188Phe (c.563C>T) pathogenic?

BMP10 p.Ser188Phe (c.563C>T) is classified Uncertain significance in BMP10 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-26). AlphaMissense: likely benign (0.3292); Absent from gnomAD v4.1.

How common is BMP10 p.Ser188Phe (c.563C>T) in the general population?

BMP10 p.Ser188Phe (c.563C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BMP10 p.Ser188Phe (c.563C>T)?

AlphaMissense predicts likely benign (score 0.3292) — an in-silico prediction, not a clinical call.

BMP10 p.Ser188Phe

c.563C>T · VCV3261174

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3292 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3292	likely benign
REVEL	0.695	pathogenic-leaning
SaProt	LLR -10.38	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 5,470 bp · p 0.72 · regional, not allelic
Overall
CADD	27.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BMP10
Protein: p.Ser188Phe
Coding: c.563C>T
MANE Select: NM_014482
Type: single nucleotide variant
Location: chr2:68866343 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 74.74 · 8 PDB
Residue 188: 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.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-ser188phe (accessed [today's date]).

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