Is BMP2K p.Ile98Val (c.292A>G) pathogenic?

BMP2K p.Ile98Val (c.292A>G) is classified Uncertain significance in BMP2K (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-07). AlphaMissense: likely benign (0.1158); Very rare (popmax 0.00773%, sas).

How common is BMP2K p.Ile98Val (c.292A>G) in the general population?

BMP2K p.Ile98Val (c.292A>G) is very rare (popmax 0.00773%, sas) (gnomAD).

What do computational predictors say about BMP2K p.Ile98Val (c.292A>G)?

AlphaMissense predicts likely benign (score 0.1158) — an in-silico prediction, not a clinical call.

BMP2K p.Ile98Val

c.292A>G · rs533144254 · VCV3134525

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1158 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00773%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1158	likely benign
REVEL	0.26	benign-leaning
SaProt	LLR -9.97	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
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 1.01	unconstrained · MANE · 102 kb · p 0.85 · regional, not allelic
Overall
CADD	24.9	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 0.00773% South Asian · 7/90,548 alleles

Filtering AF 0.00361% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00256%

Overall 0.00373% 60/1,608,032 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00773%	12,935
East Asian	0.00669%	14,953
African / African-American	0.004%	24,970
European (non-Finnish)	0.00374%	26,707
Remaining individualsnot grpmax-eligible	0.00321%	31,161
Admixed American	0.00167%	59,734

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: BMP2K
Protein: p.Ile98Val
Coding: c.292A>G
MANE Select: NM_198892
dbSNP: rs533144254
Type: single nucleotide variant
Location: chr4:78826150 (GRCh38)
Gene constraint: LOEUF 0.768 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.52 · 5 PDB
Residue 98: the protein kinase domain; an α-helix

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-ile98val (accessed [today's date]).

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