Is BMPR1B p.Pro157Ser (c.469C>T) pathogenic?

BMPR1B p.Pro157Ser (c.469C>T) is classified Uncertain significance in BMPR1B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-28). AlphaMissense: likely benign (0.1041); Ultra-rare (popmax 0.0253%, sas); Associated with brachydactyly type A2.

What condition is associated with BMPR1B p.Pro157Ser (c.469C>T)?

BMPR1B p.Pro157Ser (c.469C>T) is associated with brachydactyly type A2, acromesomelic dysplasia 3 (ClinVar).

How common is BMPR1B p.Pro157Ser (c.469C>T) in the general population?

BMPR1B p.Pro157Ser (c.469C>T) is ultra-rare (popmax 0.0253%, sas) (gnomAD).

What do computational predictors say about BMPR1B p.Pro157Ser (c.469C>T)?

AlphaMissense predicts likely benign (score 0.1041) — an in-silico prediction, not a clinical call.

BMPR1B p.Pro157Ser

c.469C>T · rs779609471 · VCV383191

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1041 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0253%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

brachydactyly type A2

Computational evidence

Protein change
AlphaMissense	0.1041	likely benign
REVEL	0.378	indeterminate
SaProt	LLR -5.74	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.9	GERP 1.8, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 25 kb · p 0.048 · regional, not allelic
Overall
CADD	20.8	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 0.0253% South Asian · 23/91,068 alleles

Filtering AF 0.0172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0146%

Overall 0.00198% 32/1,613,246 alleles · ultra-rare exomes 29/1,460,972 · genomes 3/152,274 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0253%	3,959
Remaining individualsnot grpmax-eligible	0.0048%	20,825
European (non-Finnish)	0.000509%	196,543

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.Pro157Ser
Coding: c.469C>T
MANE Select: NM_001203
dbSNP: rs779609471
Type: single nucleotide variant
Location: chr4:95125005 (GRCh38)
Gene constraint: LOEUF 0.331 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.36 · 1 PDB

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

Disease context

brachydactyly type A2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: acromesomelic dysplasia 3

Similar variants

BMPR1B p.Pro157Arg Uncertain significance ★ ⚠ same residue
BMPR1B p.Pro157Leu 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
BMPR1B p.Asn257Asp Uncertain significance ★★ ⚠ same condition
BMPR1B p.Asp166Gly 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-pro157ser (accessed [today's date]).

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