Is BMP2 p.Pro93Leu (c.278C>T) pathogenic?

BMP2 p.Pro93Leu (c.278C>T) is classified Uncertain significance in BMP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-05-19). AlphaMissense: likely benign (0.0703); Very rare (popmax 6.2e-05%).

How common is BMP2 p.Pro93Leu (c.278C>T) in the general population?

BMP2 p.Pro93Leu (c.278C>T) is very rare (popmax 6.2e-05%) (gnomAD).

What do computational predictors say about BMP2 p.Pro93Leu (c.278C>T)?

AlphaMissense predicts likely benign (score 0.0703) — an in-silico prediction, not a clinical call.

BMP2 p.Pro93Leu

c.278C>T · VCV4944302

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0703 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0703	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -7.54	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.8	GERP 1.7, phastCons 0.99
Regional constraint	o/e 0.92	unconstrained · MANE · 8,670 bp · p 0.13 · regional, not allelic
Overall
CADD	15.24	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 6.2e-05%

Overall 6.2e-05% 1/1,611,966 alleles · very rare exomes 1/1,459,700 · genomes 0/152,266 · joint denominator

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: BMP2
Protein: p.Pro93Leu
Coding: c.278C>T
MANE Select: NM_001200
Type: single nucleotide variant
Location: chr20:6770404 (GRCh38)
Gene constraint: LOEUF 0.213 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.37 · 21 PDB
Residue 93: a UniProt-annotated variant site (in ssfsc1); the 'disordered' region

Full BMP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BMP2 p.Pro93= Likely benign ★ same residue
BMP2 p.Arg154Ter Pathogenic/Likely pathogenic ★★ same type
BMP2 p.Arg170Ter Pathogenic/Likely pathogenic ★★ same type
BMP2 p.Cys329Ter Likely pathogenic ★★ same type
BMP2 p.Gln89Ter Pathogenic/Likely pathogenic ★★ same type
BMP2 p.Glu229Ter Pathogenic/Likely pathogenic ★★ same type
BMP2 p.Ser92Ter Pathogenic/Likely pathogenic ★★ same type
BMP2 p.Ala103Thr 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/bmp2-p-pro93leu (accessed [today's date]).

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