Is BMP7 p.Val194Ile (c.580G>A) pathogenic?

BMP7 p.Val194Ile (c.580G>A) is classified Uncertain significance in BMP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-13). AlphaMissense: likely benign (0.0659); Ultra-rare (popmax 0.0549%, sas).

How common is BMP7 p.Val194Ile (c.580G>A) in the general population?

BMP7 p.Val194Ile (c.580G>A) is ultra-rare (popmax 0.0549%, sas) (gnomAD).

What do computational predictors say about BMP7 p.Val194Ile (c.580G>A)?

AlphaMissense predicts likely benign (score 0.0659) — an in-silico prediction, not a clinical call.

BMP7 p.Val194Ile

c.580G>A · VCV4801357

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0659 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0549%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0659	likely benign
REVEL	0.074	moderately benign-leaning
SaProt	LLR -5.89	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP -0.89, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 93 kb · p 0.00035 · regional, not allelic
Overall
CADD	19.01	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0549% South Asian · 50/91,056 alleles

Filtering AF 0.0427% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0385%

Overall 0.0198% 320/1,613,950 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0549%	1,821
Remaining individualsnot grpmax-eligible	0.0256%	3,906
Admixed American	0.0217%	4,617
European (non-Finnish)	0.0198%	5,043
African / African-American	0.008%	12,505
East Asian	0.00223%	44,876

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: BMP7
Protein: p.Val194Ile
Coding: c.580G>A
MANE Select: NM_001719
Type: single nucleotide variant
Location: chr20:57228260 (GRCh38)
Gene constraint: LOEUF 0.523 · pLI 0.96 (gnomAD)
Structure: AlphaFold pLDDT 76.50 · 4 PDB

Full BMP7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BMP7 p.Arg150His Uncertain significance ★★ ⚠ same type
BMP7 p.Arg267Gln Uncertain significance ★★ ⚠ same type
BMP7 p.His241Tyr Uncertain significance ★★ ⚠ same type
BMP7 p.Ile386Val Uncertain significance ★★ ⚠ same type
BMP7 p.Leu160Phe Uncertain significance ★★ ⚠ same type
BMP7 p.Pro116Ser Uncertain significance ★★ ⚠ same type
BMP7 p.Ser248Leu Uncertain significance ★★ ⚠ same type
BMP7 p.Thr251Met Uncertain significance ★★ ⚠ same type

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/bmp7-p-val194ile (accessed [today's date]).

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