Is KDM5C p.Arg599Cys (c.1795C>T) pathogenic?

KDM5C p.Arg599Cys (c.1795C>T) is classified Pathogenic/Likely pathogenic in KDM5C (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-03-22). AlphaMissense: likely pathogenic (0.9705); Very rare (popmax 9.11e-05%); Associated with syndromic X-linked intellectual disability Claes-Jensen type.

What condition is associated with KDM5C p.Arg599Cys (c.1795C>T)?

KDM5C p.Arg599Cys (c.1795C>T) is associated with syndromic X-linked intellectual disability Claes-Jensen type (ClinVar).

How common is KDM5C p.Arg599Cys (c.1795C>T) in the general population?

KDM5C p.Arg599Cys (c.1795C>T) is very rare (popmax 9.11e-05%) (gnomAD).

What do computational predictors say about KDM5C p.Arg599Cys (c.1795C>T)?

AlphaMissense predicts likely pathogenic (score 0.9705) — an in-silico prediction, not a clinical call.

KDM5C p.Arg599Cys

c.1795C>T · rs1556842184 · VCV559937

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9705 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 9.11e-05%)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

syndromic X-linked intellectual disability Claes-Jensen type

Computational evidence

Protein change
AlphaMissense	0.9705	likely pathogenic ✓ concordant with ClinVar
REVEL	0.693	pathogenic-leaning
SaProt	LLR -13.99	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 8.6	GERP 2.8, phastCons 1
Regional constraint	o/e 0.20	constrained · MANE · 10 kb · p 1.4e-30 · regional, not allelic
Overall
CADD	23.0	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 9.11e-05%

Overall 9.11e-05% 1/1,097,986 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: KDM5C
Protein: p.Arg599Cys
Coding: c.1795C>T
MANE Select: NM_004187
dbSNP: rs1556842184
Type: single nucleotide variant
Location: chrX:53201925 (GRCh38)
Structure: AlphaFold pLDDT 72.50 · 2 PDB
Residue 599: the jmjc domain

Full KDM5C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

syndromic X-linked intellectual disability Claes-Jensen type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KDM5C p.Arg332Ter Pathogenic ★★ same condition
KDM5C p.Arg681Ter Pathogenic/Likely pathogenic ★★ same condition
KDM5C p.Arg750Trp Likely pathogenic ★★ same condition
KDM5C p.Arg828Ter Pathogenic ★★ same condition
KDM5C p.Arg943Ter Pathogenic/Likely pathogenic ★★ same condition
KDM5C p.Gln1020Ter Pathogenic ★★ same condition
KDM5C p.Gln199Ter Pathogenic ★★ same condition
KDM5C p.Gln970Ter 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/kdm5c-p-arg599cys (accessed [today's date]).

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