Is BMPR1B p.Arg413Ser (c.1239A>T) pathogenic?

BMPR1B p.Arg413Ser (c.1239A>T) is classified Conflicting classifications of pathogenicity in BMPR1B (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-07-10). AlphaMissense: likely pathogenic (0.9731); Ultra-rare (popmax 0.0847%, eas); Associated with acromesomelic dysplasia 3.

What condition is associated with BMPR1B p.Arg413Ser (c.1239A>T)?

BMPR1B p.Arg413Ser (c.1239A>T) is associated with acromesomelic dysplasia 3, brachydactyly type A2, brachydactyly type A1D (ClinVar).

How common is BMPR1B p.Arg413Ser (c.1239A>T) in the general population?

BMPR1B p.Arg413Ser (c.1239A>T) is ultra-rare (popmax 0.0847%, eas) (gnomAD).

What do computational predictors say about BMPR1B p.Arg413Ser (c.1239A>T)?

AlphaMissense predicts likely pathogenic (score 0.9731) — an in-silico prediction, not a clinical call.

BMPR1B p.Arg413Ser

c.1239A>T · rs186299744 · VCV1914196

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9731 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0847%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

acromesomelic dysplasia 3

Computational evidence

Protein change
AlphaMissense	0.9731	likely pathogenic
REVEL	0.888	moderately pathogenic-leaning
SaProt	LLR -13.34	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>G here scores Δ0.75 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.2	GERP 0.33, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 5,884 bp · p 0.0012 · regional, not allelic
Overall
CADD	24.9	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 0.0847% East Asian · 38/44,874 alleles

Filtering AF 0.0634% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.056%

Overall 0.00273% 44/1,613,918 alleles · ultra-rare exomes 38/1,461,694 · genomes 6/152,224 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0847%	1,181
South Asian	0.00439%	22,770
Remaining individualsnot grpmax-eligible	0.0016%	62,502
European (non-Finnish)	8.48e-05%	1,179,884

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.Arg413Ser
Coding: c.1239A>T
MANE Select: NM_001203
dbSNP: rs186299744
Type: single nucleotide variant
Location: chr4:95148910 (GRCh38)
Gene constraint: LOEUF 0.331 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.36 · 1 PDB
Residue 413: 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 brachydactyly type A1D

Similar variants

BMPR1B p.Arg413Thr 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
BMPR1B p.Asp280Asn 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-arg413ser (accessed [today's date]).

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