Is KDM2B p.Pro972Ala (c.2914C>G) pathogenic?

KDM2B p.Pro972Ala (c.2914C>G) is classified Uncertain significance in KDM2B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-27). AlphaMissense: likely benign (0.0806); Absent from gnomAD v4.1.

How common is KDM2B p.Pro972Ala (c.2914C>G) in the general population?

KDM2B p.Pro972Ala (c.2914C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KDM2B p.Pro972Ala (c.2914C>G)?

AlphaMissense predicts likely benign (score 0.0806) — an in-silico prediction, not a clinical call.

KDM2B p.Pro972Ala

c.2914C>G · VCV3361464

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0806 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0806	likely benign
REVEL	0.191	benign-leaning
SaProt	LLR -6.55	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 9.8	GERP 0.93, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 1,864 bp · p 0.44 · regional, not allelic
Overall
CADD	24.8	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: KDM2B
Protein: p.Pro972Ala
Coding: c.2914C>G
MANE Select: NM_032590
Type: single nucleotide variant
Location: chr12:121442527 (GRCh38)
Gene constraint: LOEUF 0.266 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.20 · 4 PDB
Residue 972: the 'disordered' region

Full KDM2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KDM2B p.Arg614Pro Pathogenic/Likely pathogenic ★★ same type
KDM2B p.Cys616Arg Pathogenic/Likely pathogenic ★★ same type
KDM2B p.Gly638Asp Pathogenic ★★ same type
KDM2B p.Arg1124Gln Uncertain significance ★★ ⚠ same type
KDM2B p.Arg294Gln Uncertain significance ★★ ⚠ same type
KDM2B p.Arg612Gln Uncertain significance ★★ ⚠ same type
KDM2B p.Asn742Lys Uncertain significance ★★ ⚠ same type
KDM2B p.Glu922Lys 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/kdm2b-p-pro972ala (accessed [today's date]).

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