Is BMP4 p.Arg84= (c.252G>A) pathogenic?

BMP4 p.Arg84= (c.252G>A) is classified Likely benign in BMP4 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-11-05). Ultra-rare (popmax 0.0493%, mid); Associated with microphthalmia with brain and digit anomalies.

What condition is associated with BMP4 p.Arg84= (c.252G>A)?

BMP4 p.Arg84= (c.252G>A) is associated with microphthalmia with brain and digit anomalies, orofacial cleft 11 (ClinVar).

How common is BMP4 p.Arg84= (c.252G>A) in the general population?

BMP4 p.Arg84= (c.252G>A) is ultra-rare (popmax 0.0493%, mid) (gnomAD).

BMP4 p.Arg84=

c.252G>A · rs781435238 · VCV434517

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0493%, mid)

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 3.2	GERP 1.7, phastCons 1
Overall
CADD	13.61	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0493% Middle Eastern · 3/6,084 alleles

Filtering AF 0.0237% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0205%

Overall 0.00453% 73/1,612,382 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0493%	2,028
South Asian	0.0329%	3,036
Admixed American	0.005%	20,004
Remaining individualsnot grpmax-eligible	0.0048%	20,825
European (non-Finnish)	0.00288%	34,707

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.Arg84=
Coding: c.252G>A
MANE Select: NM_001202
dbSNP: rs781435238
Type: single nucleotide variant
Location: chr14:53951971 (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.Arg84Gln Uncertain significance ★★ ⚠ same residue
BMP4 p.Arg84Trp 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

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-arg84 (accessed [today's date]).

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