Is BMP4 p.Pro342= (c.1026C>G) pathogenic?

BMP4 p.Pro342= (c.1026C>G) is classified Likely benign in BMP4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-12-15). Ultra-rare (popmax 0.0223%, eas); Associated with BMP4-related disorder.

What condition is associated with BMP4 p.Pro342= (c.1026C>G)?

BMP4 p.Pro342= (c.1026C>G) is associated with BMP4-related disorder (ClinVar).

How common is BMP4 p.Pro342= (c.1026C>G) in the general population?

BMP4 p.Pro342= (c.1026C>G) is ultra-rare (popmax 0.0223%, eas) (gnomAD).

BMP4 p.Pro342=

c.1026C>G · rs752087708 · VCV3049473

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0223%, eas)

Conditions

BMP4-related disorder

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 1.8	GERP -0.2, phastCons 1
Overall
CADD	9.888	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0223% East Asian · 10/44,904 alleles

Filtering AF 0.012% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00916%

Overall 0.000681% 11/1,614,150 alleles · ultra-rare exomes 10/1,461,890 · genomes 1/152,260 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0223%	4,490
Remaining individualsnot grpmax-eligible	0.0016%	62,490

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: BMP4
Protein: p.Pro342=
Coding: c.1026C>G
MANE Select: NM_001202
dbSNP: rs752087708
Type: single nucleotide variant
Location: chr14:53950233 (GRCh38)
Gene constraint: LOEUF 0.258 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.12

Full BMP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

BMP4-related disorder

Similar variants

BMP4 p.Thr30Met Uncertain significance ★★ ⚠ same condition
BMP4 c.-97G>T Uncertain significance ★ same condition
BMP4 p.Arg109His Uncertain significance ★ ⚠ same condition
BMP4 c.-347A>T Uncertain significance same condition
BMP4 c.-365C>G Uncertain significance same condition
BMP4 p.Gln243His Uncertain significance ⚠ same condition
BMP4 p.Gly174Ser Uncertain significance ⚠ same condition
BMP4 p.Leu384Val 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/bmp4-p-pro342 (accessed [today's date]).

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