Is BMPR1B p.Pro368Ser (c.1102C>T) pathogenic?

BMPR1B p.Pro368Ser (c.1102C>T) is classified Conflicting classifications of pathogenicity in BMPR1B (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-12-23). AlphaMissense: likely benign (0.1472); Rare (popmax 0.124%, sas); Associated with brachydactyly.

What condition is associated with BMPR1B p.Pro368Ser (c.1102C>T)?

BMPR1B p.Pro368Ser (c.1102C>T) is associated with brachydactyly, brachydactyly type A2, acromesomelic dysplasia 3 (ClinVar).

How common is BMPR1B p.Pro368Ser (c.1102C>T) in the general population?

BMPR1B p.Pro368Ser (c.1102C>T) is rare (popmax 0.124%, sas) (gnomAD).

What do computational predictors say about BMPR1B p.Pro368Ser (c.1102C>T)?

AlphaMissense predicts likely benign (score 0.1472) — an in-silico prediction, not a clinical call.

BMPR1B p.Pro368Ser

c.1102C>T · rs577188671 · VCV350123

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1472 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.124%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

brachydactyly

Computational evidence

Protein change
AlphaMissense	0.1472	likely benign
REVEL	0.161	moderately benign-leaning
SaProt	LLR -4.94	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
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	21.4	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 0.124% South Asian · 113/91,080 alleles

Filtering AF 0.105% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0985%

Overall 0.00874% 141/1,614,002 alleles · rare exomes 129/1,461,710 · genomes 12/152,292 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.124%	806
Middle Eastern	0.066%	1,515
East Asian	0.0134%	7,479
Remaining individualsnot grpmax-eligible	0.0128%	7,812
European (non-Finnish)	0.000848%	117,993

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.Pro368Ser
Coding: c.1102C>T
MANE Select: NM_001203
dbSNP: rs577188671
Type: single nucleotide variant
Location: chr4:95148773 (GRCh38)
Gene constraint: LOEUF 0.331 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.36 · 1 PDB
Residue 368: the protein kinase domain

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

Disease context

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

Also linked: brachydactyly type A2 acromesomelic dysplasia 3

Similar variants

BMPR1B c.585+1G>C Likely pathogenic ★★ same condition
BMPR1B p.Arg486Trp Pathogenic ★★ same condition
BMPR1B c.*828T>G Uncertain significance ★★ same condition
BMPR1B c.*83C>G Uncertain significance ★★ 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-pro368ser (accessed [today's date]).

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