Is BMP4 p.Pro71= (c.213G>T) pathogenic?

BMP4 p.Pro71= (c.213G>T) is classified Benign in BMP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-02). Rare (popmax 0.158%, sas); Associated with microphthalmia with brain and digit anomalies.

What condition is associated with BMP4 p.Pro71= (c.213G>T)?

BMP4 p.Pro71= (c.213G>T) is associated with microphthalmia with brain and digit anomalies, orofacial cleft 11 (ClinVar).

How common is BMP4 p.Pro71= (c.213G>T) in the general population?

BMP4 p.Pro71= (c.213G>T) is rare (popmax 0.158%, sas) (gnomAD).

BMP4 p.Pro71=

c.213G>T · rs539120233 · VCV2163081

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.158%, sas)

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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.5	GERP 1.7, phastCons 1
Overall
CADD	14.81	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.158% South Asian · 144/91,090 alleles

Filtering AF 0.137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.129%

Overall 0.00936% 151/1,613,850 alleles · rare exomes 141/1,461,510 · genomes 10/152,340 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.158%	633
Middle Eastern	0.033%	3,031
Remaining individualsnot grpmax-eligible	0.008%	12,501

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.Pro71=
Coding: c.213G>T
MANE Select: NM_001202
dbSNP: rs539120233
Type: single nucleotide variant
Location: chr14:53952010 (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.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
BMP4 p.Arg245Trp 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-pro71 (accessed [today's date]).

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