Is BMPR1B p.Asp384= (c.1152C>T) pathogenic?

BMPR1B p.Asp384= (c.1152C>T) is classified Likely benign in BMPR1B (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-02-10). Ultra-rare (popmax 0.0329%, mid); Associated with brachydactyly type A2.

What condition is associated with BMPR1B p.Asp384= (c.1152C>T)?

BMPR1B p.Asp384= (c.1152C>T) is associated with brachydactyly type A2, acromesomelic dysplasia 3 (ClinVar).

How common is BMPR1B p.Asp384= (c.1152C>T) in the general population?

BMPR1B p.Asp384= (c.1152C>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

BMPR1B p.Asp384=

c.1152C>T · rs375476260 · VCV1611545

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Conditions

brachydactyly type A2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.3	GERP -5.3
Overall
CADD	2.491	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,082 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00241%

Overall 0.00112% 18/1,613,838 alleles · ultra-rare exomes 15/1,461,752 · genomes 3/152,086 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,041
Admixed American	0.00834%	11,997
African / African-American	0.00801%	12,479
East Asian	0.00669%	14,959
European (non-Finnish)	0.00017%	589,967

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.Asp384=
Coding: c.1152C>T
MANE Select: NM_001203
dbSNP: rs375476260
Type: single nucleotide variant
Location: chr4:95148823 (GRCh38)
Gene constraint: LOEUF 0.331 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.36 · 1 PDB
Residue 384: the protein kinase domain

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 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-asp384 (accessed [today's date]).

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