Is KDM5B p.Pro263Ser (c.787C>T) pathogenic?

KDM5B p.Pro263Ser (c.787C>T) is classified Pathogenic in KDM5B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-04-01). AlphaMissense: likely benign (0.0667); Absent from gnomAD v4.1; Associated with intellectual disability, autosomal recessive 65.

What condition is associated with KDM5B p.Pro263Ser (c.787C>T)?

KDM5B p.Pro263Ser (c.787C>T) is associated with intellectual disability, autosomal recessive 65 (ClinVar).

How common is KDM5B p.Pro263Ser (c.787C>T) in the general population?

KDM5B p.Pro263Ser (c.787C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KDM5B p.Pro263Ser (c.787C>T)?

AlphaMissense predicts likely benign (score 0.0667) — an in-silico prediction, not a clinical call.

KDM5B p.Pro263Ser

c.787C>T · rs375695605 · VCV560602

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0667 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability, autosomal recessive 65

Computational evidence

Protein change
AlphaMissense	0.0667	likely benign ⚠ discordant with ClinVar
REVEL	0.195	benign-leaning
SaProt	LLR -5.26	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 3.7	GERP 1, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 46 kb · p 0.3 · regional, not allelic
Overall
CADD	17.29	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

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.Pro263Ser
Coding: c.787C>T
MANE Select: NM_006618
dbSNP: rs375695605
Type: single nucleotide variant
Location: chr1:202764070 (GRCh38)
Gene constraint: LOEUF 0.858 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 72.52 · 56 PDB

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-pro263ser (accessed [today's date]).

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