Is BMPR1B p.Phe392Val (c.1174T>G) pathogenic?

BMPR1B p.Phe392Val (c.1174T>G) is classified Uncertain significance in BMPR1B (ClinVar, Single submitter, 1 submitter; last evaluated 2020-04-07). AlphaMissense: likely pathogenic (0.9673); Very rare (popmax 8.47e-05%, nfe); Associated with brachydactyly type A2.

What condition is associated with BMPR1B p.Phe392Val (c.1174T>G)?

BMPR1B p.Phe392Val (c.1174T>G) is associated with brachydactyly type A2, acromesomelic dysplasia 3 (ClinVar).

How common is BMPR1B p.Phe392Val (c.1174T>G) in the general population?

BMPR1B p.Phe392Val (c.1174T>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about BMPR1B p.Phe392Val (c.1174T>G)?

AlphaMissense predicts likely pathogenic (score 0.9673) — an in-silico prediction, not a clinical call.

BMPR1B p.Phe392Val

c.1174T>G · rs1464900722 · VCV1060472

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9673 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

brachydactyly type A2

Computational evidence

Protein change
AlphaMissense	0.9673	likely pathogenic
REVEL	0.596	indeterminate
SaProt	LLR -14.26	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.7, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 5,884 bp · p 0.0012 · regional, not allelic
Overall
CADD	30.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 8.47e-05% European (non-Finnish) · 1/1,179,962 alleles

Overall 6.2e-05% 1/1,613,940 alleles · very rare exomes 0/1,461,784 · genomes 1/152,156 · joint denominator

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.Phe392Val
Coding: c.1174T>G
MANE Select: NM_001203
dbSNP: rs1464900722
Type: single nucleotide variant
Location: chr4:95148845 (GRCh38)
Gene constraint: LOEUF 0.331 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.36 · 1 PDB
Residue 392: 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-phe392val (accessed [today's date]).

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