Is BMP5 p.Leu142Pro (c.425T>C) pathogenic?

BMP5 p.Leu142Pro (c.425T>C) is classified Uncertain significance in BMP5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-14). AlphaMissense: likely benign (0.1953); Absent from gnomAD v4.1.

How common is BMP5 p.Leu142Pro (c.425T>C) in the general population?

BMP5 p.Leu142Pro (c.425T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BMP5 p.Leu142Pro (c.425T>C)?

AlphaMissense predicts likely benign (score 0.1953) — an in-silico prediction, not a clinical call.

BMP5 p.Leu142Pro

c.425T>C · rs2481899630 · VCV2624253

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1953 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1953	likely benign
REVEL	0.715	pathogenic-leaning
SaProt	LLR -5.56	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 119 kb · p 0.39 · regional, not allelic
Overall
CADD	27.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BMP5
Protein: p.Leu142Pro
Coding: c.425T>C
MANE Select: NM_021073
dbSNP: rs2481899630
Type: single nucleotide variant
Location: chr6:55874441 (GRCh38)
Gene constraint: LOEUF 0.711 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.85

Full BMP5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BMP5 p.Leu142Val Uncertain significance ★ ⚠ same residue
BMP5 p.Ala103Thr Uncertain significance ★ ⚠ same type
BMP5 p.Ala118Asp Uncertain significance ★ ⚠ same type
BMP5 p.Ala25Thr Uncertain significance ★ ⚠ same type
BMP5 p.Ala307Glu Uncertain significance ★ same type
BMP5 p.Ala317Val Uncertain significance ★ same type
BMP5 p.Ala74Thr Uncertain significance ★ ⚠ same type
BMP5 p.Ala77Val 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/bmp5-p-leu142pro (accessed [today's date]).

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