Is BMPR1B p.Phe242Ser (c.725T>C) pathogenic?

BMPR1B p.Phe242Ser (c.725T>C) is classified Uncertain significance in BMPR1B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-10). AlphaMissense: likely pathogenic (0.8724); Ultra-rare (popmax 0.01%, amr); Associated with acromesomelic dysplasia 3.

What condition is associated with BMPR1B p.Phe242Ser (c.725T>C)?

BMPR1B p.Phe242Ser (c.725T>C) is associated with acromesomelic dysplasia 3, brachydactyly type A2 (ClinVar).

How common is BMPR1B p.Phe242Ser (c.725T>C) in the general population?

BMPR1B p.Phe242Ser (c.725T>C) is ultra-rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about BMPR1B p.Phe242Ser (c.725T>C)?

AlphaMissense predicts likely pathogenic (score 0.8724) — an in-silico prediction, not a clinical call.

BMPR1B p.Phe242Ser

c.725T>C · VCV3992040

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8724 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

acromesomelic dysplasia 3

Computational evidence

Protein change
AlphaMissense	0.8724	likely pathogenic
REVEL	0.382	indeterminate
SaProt	LLR -8.37	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 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 25 kb · p 0.048 · regional, not allelic
Overall
CADD	28.6	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 0.01% Admixed American · 6/59,950 alleles

Filtering AF 0.00429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.0013% 21/1,613,868 alleles · ultra-rare exomes 16/1,461,712 · genomes 5/152,156 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	9,992
East Asian	0.00446%	22,441
South Asian	0.00329%	30,363
Remaining individualsnot grpmax-eligible	0.0032%	31,241
European (non-Finnish)	0.000678%	147,492

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: BMPR1B
Protein: p.Phe242Ser
Coding: c.725T>C
MANE Select: NM_001203
Type: single nucleotide variant
Location: chr4:95130001 (GRCh38)
Gene constraint: LOEUF 0.331 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.36 · 1 PDB
Residue 242: an α-helix; the protein kinase domain

Full BMPR1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

acromesomelic dysplasia 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: brachydactyly type A2

Similar variants

BMPR1B p.Phe242Leu Uncertain significance ★★ ⚠ same residue
BMPR1B p.Phe242Cys Uncertain significance ★ ⚠ same residue
BMPR1B p.Phe242Tyr Uncertain significance ★ same residue
BMPR1B p.Phe242Val Uncertain significance ★ ⚠ same residue
BMPR1B c.585+1G>C Likely pathogenic ★★ same condition
BMPR1B p.Arg486Trp Pathogenic ★★ same condition
BMPR1B p.Arg412Gly Uncertain significance ★★ ⚠ same condition
BMPR1B p.Arg91Ile Uncertain significance ★★ ⚠ same condition

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/bmpr1b-p-phe242ser (accessed [today's date]).

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