Is KDM2B p.Ile62Phe (c.184A>T) pathogenic?

KDM2B p.Ile62Phe (c.184A>T) is classified Uncertain significance in KDM2B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-14). AlphaMissense: ambiguous (0.4409); Very rare (popmax 0.00127%, nfe); Associated with Inborn genetic diseases.

What condition is associated with KDM2B p.Ile62Phe (c.184A>T)?

KDM2B p.Ile62Phe (c.184A>T) is associated with Inborn genetic diseases (ClinVar).

How common is KDM2B p.Ile62Phe (c.184A>T) in the general population?

KDM2B p.Ile62Phe (c.184A>T) is very rare (popmax 0.00127%, nfe) (gnomAD).

What do computational predictors say about KDM2B p.Ile62Phe (c.184A>T)?

AlphaMissense predicts ambiguous (score 0.4409) — an in-silico prediction, not a clinical call.

KDM2B p.Ile62Phe

c.184A>T · VCV3863406

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4409 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00127%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4409	ambiguous
REVEL	0.172	moderately benign-leaning
SaProt	LLR -6.99	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 6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.48	unconstrained · MANE · 66 kb · p 2.6e-28 · regional, not allelic
Overall
CADD	24.4	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

Grpmax group 0.00127% European (non-Finnish) · 15/1,179,630 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.00103% 15/1,460,644 alleles · very rare

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: KDM2B
Protein: p.Ile62Phe
Coding: c.184A>T
MANE Select: NM_032590
Type: single nucleotide variant
Location: chr12:121578889 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RNF34 p.Cys62Gly Uncertain significance ★ ⚠ same residue
KDM2B p.Arg294Gln Uncertain significance ★★ ⚠ same condition
KDM2B p.Arg612Gln Uncertain significance ★★ ⚠ same condition
KDM2B p.Asn742Lys Uncertain significance ★★ ⚠ same condition
KDM2B p.Glu922Lys Uncertain significance ★★ ⚠ same condition
KDM2B p.Val157Met Uncertain significance ★★ ⚠ same condition
KDM2B p.Glu894Lys Likely benign ★★ ⚠ same condition
KDM2B p.Cys616Phe Pathogenic ★ same condition

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-ile62phe (accessed [today's date]).

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