Is BMP7 p.Leu160Pro (c.479T>C) pathogenic?

BMP7 p.Leu160Pro (c.479T>C) is classified Uncertain significance in BMP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-02). AlphaMissense: likely pathogenic (0.9553); Very rare (popmax 0.00223%, eas).

How common is BMP7 p.Leu160Pro (c.479T>C) in the general population?

BMP7 p.Leu160Pro (c.479T>C) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about BMP7 p.Leu160Pro (c.479T>C)?

AlphaMissense predicts likely pathogenic (score 0.9553) — an in-silico prediction, not a clinical call.

BMP7 p.Leu160Pro

c.479T>C · VCV4214324

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9553 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9553	likely pathogenic
REVEL	0.852	moderately pathogenic-leaning
SaProt	LLR -15.49	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 93 kb · p 0.00035 · regional, not allelic
Overall
CADD	28.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00223% East Asian · 1/44,880 alleles

Overall 0.000137% 2/1,461,890 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,880
European (non-Finnish)	8.47e-05%	1,180,040

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.Leu160Pro
Coding: c.479T>C
MANE Select: NM_001719
Type: single nucleotide variant
Location: chr20:57228361 (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.Leu160Phe Uncertain significance ★★ ⚠ same residue
BMP7 p.Leu160Val Uncertain significance ★ ⚠ same residue
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.Pro116Ser Uncertain significance ★★ ⚠ same type
BMP7 p.Ser248Leu 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-leu160pro (accessed [today's date]).

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