Is BMP4 p.Val205= (c.615C>A) pathogenic?

BMP4 p.Val205= (c.615C>A) is classified Likely benign in BMP4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-22). Ultra-rare (popmax 0.0467%, afr); Associated with microphthalmia with brain and digit anomalies.

What condition is associated with BMP4 p.Val205= (c.615C>A)?

BMP4 p.Val205= (c.615C>A) is associated with microphthalmia with brain and digit anomalies, orofacial cleft 11 (ClinVar).

How common is BMP4 p.Val205= (c.615C>A) in the general population?

BMP4 p.Val205= (c.615C>A) is ultra-rare (popmax 0.0467%, afr) (gnomAD).

BMP4 p.Val205=

c.615C>A · rs777036089 · VCV2922391

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0467%, afr)

Conditions

microphthalmia with brain and digit anomalies

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 4	GERP -2.9, phastCons 1
Overall
CADD	10.07	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0467% African / African-American · 35/74,946 alleles

Filtering AF 0.0345% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0303%

Overall 0.00217% 35/1,614,124 alleles · ultra-rare

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.Val205=
Coding: c.615C>A
MANE Select: NM_001202
dbSNP: rs777036089
Type: single nucleotide variant
Location: chr14:53950644 (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

microphthalmia with brain and digit anomalies — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: orofacial cleft 11

Similar variants

BMP4 p.Val205Ala Uncertain significance ⚠ same residue
BMP4 p.Arg198Ter Pathogenic ★★ same condition
BMP4 p.Arg113Gln Uncertain significance ★★ ⚠ same condition
BMP4 p.Arg159Trp Uncertain significance ★★ ⚠ same condition
BMP4 p.Arg162Trp Uncertain significance ★★ ⚠ same condition
BMP4 p.Arg177His Uncertain significance ★★ ⚠ same condition
BMP4 p.Arg211Gln Uncertain significance ★★ ⚠ same condition
BMP4 p.Arg223His 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-val205 (accessed [today's date]).

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