Is BMPR1B p.Pro112Ser (c.334C>T) pathogenic?

BMPR1B p.Pro112Ser (c.334C>T) is classified Likely benign in BMPR1B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-23). AlphaMissense: likely benign (0.1407); Ultra-rare (popmax 0.0167%, amr); Associated with acromesomelic dysplasia 3.

What condition is associated with BMPR1B p.Pro112Ser (c.334C>T)?

BMPR1B p.Pro112Ser (c.334C>T) is associated with acromesomelic dysplasia 3, brachydactyly type A2 (ClinVar).

How common is BMPR1B p.Pro112Ser (c.334C>T) in the general population?

BMPR1B p.Pro112Ser (c.334C>T) is ultra-rare (popmax 0.0167%, amr) (gnomAD).

What do computational predictors say about BMPR1B p.Pro112Ser (c.334C>T)?

AlphaMissense predicts likely benign (score 0.1407) — an in-silico prediction, not a clinical call.

BMPR1B p.Pro112Ser

c.334C>T · rs1225550138 · VCV1010451

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1407 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

acromesomelic dysplasia 3

Computational evidence

Protein change
AlphaMissense	0.1407	likely benign
REVEL	0.562	indeterminate
SaProt	LLR -11.79	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.6, phastCons 1
Regional constraint	o/e 0.50	unconstrained · MANE · 8,118 bp · p 0.0016 · regional, not allelic
Overall
CADD	24.6	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 0.0167% Admixed American · 10/59,976 alleles

Filtering AF 0.009% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00682%

Overall 0.000682% 11/1,612,150 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0167%	5,998
Remaining individualsnot grpmax-eligible	0.0016%	62,428

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.Pro112Ser
Coding: c.334C>T
MANE Select: NM_001203
dbSNP: rs1225550138
Type: single nucleotide variant
Location: chr4:95115772 (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

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

Also linked: brachydactyly type A2

Similar variants

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
BMPR1B p.Asp280Asn Uncertain significance ★★ same condition
BMPR1B p.Asp365Asn 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-pro112ser (accessed [today's date]).

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