Is BMP5 p.Pro70Leu (c.209C>T) pathogenic?

BMP5 p.Pro70Leu (c.209C>T) is classified Uncertain significance in BMP5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-06). AlphaMissense: likely benign (0.1278); Absent from gnomAD v4.1.

How common is BMP5 p.Pro70Leu (c.209C>T) in the general population?

BMP5 p.Pro70Leu (c.209C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BMP5 p.Pro70Leu (c.209C>T)?

AlphaMissense predicts likely benign (score 0.1278) — an in-silico prediction, not a clinical call.

BMP5 p.Pro70Leu

c.209C>T · VCV4646219

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1278 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1278	likely benign
REVEL	0.413	indeterminate
SaProt	LLR -6.73	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 2.5, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 119 kb · p 0.39 · regional, not allelic
Overall
CADD	24.0	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

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.Pro70Leu
Coding: c.209C>T
MANE Select: NM_021073
Type: single nucleotide variant
Location: chr6:55874657 (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.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
BMP5 p.Arg125Cys 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-pro70leu (accessed [today's date]).

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