Is BMP2K p.Pro363Gln (c.1088C>A) pathogenic?

BMP2K p.Pro363Gln (c.1088C>A) is classified Uncertain significance in BMP2K (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-19). AlphaMissense: ambiguous (0.4835); Absent from gnomAD v4.1.

How common is BMP2K p.Pro363Gln (c.1088C>A) in the general population?

BMP2K p.Pro363Gln (c.1088C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BMP2K p.Pro363Gln (c.1088C>A)?

AlphaMissense predicts ambiguous (score 0.4835) — an in-silico prediction, not a clinical call.

BMP2K p.Pro363Gln

c.1088C>A · VCV4214263

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4835 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4835	ambiguous
REVEL	0.194	benign-leaning
SaProt	LLR -9.90	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.4, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 102 kb · p 0.85 · regional, not allelic
Overall
CADD	24.8	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: BMP2K
Protein: p.Pro363Gln
Coding: c.1088C>A
MANE Select: NM_198892
Type: single nucleotide variant
Location: chr4:78865577 (GRCh38)
Gene constraint: LOEUF 0.768 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.52 · 5 PDB
Residue 363: the 'disordered' region

Full BMP2K gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BMP2K p.Gln1161Ter Benign/Likely benign ★★ same type
BMP2K p.Ala165Val Uncertain significance ★ ⚠ same type
BMP2K p.Ala231Ser Uncertain significance ★ ⚠ same type
BMP2K p.Ala393Thr Uncertain significance ★ ⚠ same type
BMP2K p.Arg179Trp Uncertain significance ★ ⚠ same type
BMP2K p.Arg285Cys Uncertain significance ★ ⚠ same type
BMP2K p.Arg69Cys Uncertain significance ★ same type
BMP2K p.Arg69His 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/bmp2k-p-pro363gln (accessed [today's date]).

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