Is KDM2B p.Arg136Gln (c.407G>A) pathogenic?

KDM2B p.Arg136Gln (c.407G>A) is classified Uncertain significance in KDM2B (ClinVar, Single submitter, 1 submitter; last evaluated 2026-08-06). AlphaMissense: likely pathogenic (0.9719); Absent from gnomAD v4.1.

How common is KDM2B p.Arg136Gln (c.407G>A) in the general population?

KDM2B p.Arg136Gln (c.407G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KDM2B p.Arg136Gln (c.407G>A)?

AlphaMissense predicts likely pathogenic (score 0.9719) — an in-silico prediction, not a clinical call.

KDM2B p.Arg136Gln

c.407G>A · VCV3363216

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9719 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9719	likely pathogenic
REVEL	0.616	indeterminate
SaProt	LLR -13.51	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, phastCons 1
Regional constraint	o/e 0.48	unconstrained · MANE · 66 kb · p 2.6e-28 · regional, not allelic
Overall
CADD	26.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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.Arg136Gln
Coding: c.407G>A
MANE Select: NM_032590
Type: single nucleotide variant
Location: chr12:121549629 (GRCh38)
Gene constraint: LOEUF 0.266 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.20 · 4 PDB

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-arg136gln (accessed [today's date]).

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