Is KDM5B p.Pro67Gln (c.200C>A) pathogenic?

KDM5B p.Pro67Gln (c.200C>A) is classified Uncertain significance in KDM5B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-01). AlphaMissense: likely pathogenic (0.9745); Absent from gnomAD v4.1; Associated with intellectual disability, autosomal recessive 65.

What condition is associated with KDM5B p.Pro67Gln (c.200C>A)?

KDM5B p.Pro67Gln (c.200C>A) is associated with intellectual disability, autosomal recessive 65 (ClinVar).

How common is KDM5B p.Pro67Gln (c.200C>A) in the general population?

KDM5B p.Pro67Gln (c.200C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KDM5B p.Pro67Gln (c.200C>A)?

AlphaMissense predicts likely pathogenic (score 0.9745) — an in-silico prediction, not a clinical call.

KDM5B p.Pro67Gln

c.200C>A · VCV3764551

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9745 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability, autosomal recessive 65

Computational evidence

Protein change
AlphaMissense	0.9745	likely pathogenic
REVEL	0.873	moderately pathogenic-leaning
SaProt	LLR -15.11	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 46 kb · p 0.3 · regional, not allelic
Overall
CADD	27.8	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: KDM5B
Protein: p.Pro67Gln
Coding: c.200C>A
MANE Select: NM_006618
Type: single nucleotide variant
Location: chr1:202808106 (GRCh38)
Gene constraint: LOEUF 0.858 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 72.52 · 56 PDB
Residue 67: the jmjn domain; an α-helix

Full KDM5B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual disability, autosomal recessive 65 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KDM5B c.2945+1G>A Likely pathogenic ★★ same condition
KDM5B p.Arg1047Ter Pathogenic/Likely pathogenic ★★ same condition
KDM5B p.Arg1214Ter Likely pathogenic ★★ same condition
KDM5B p.Arg1426Ter Pathogenic/Likely pathogenic ★★ same condition
KDM5B p.Arg299Ter Pathogenic/Likely pathogenic ★★ same condition
KDM5B p.Arg441Ter Pathogenic/Likely pathogenic ★★ same condition
KDM5B p.Arg570Ter Pathogenic/Likely pathogenic ★★ same condition
KDM5B p.Arg98Cys Uncertain significance ★★ ⚠ 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/kdm5b-p-pro67gln (accessed [today's date]).

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