Is KDM5C p.Val583Phe (c.1747G>T) pathogenic?

KDM5C p.Val583Phe (c.1747G>T) is classified Likely pathogenic in KDM5C (ClinVar, Single submitter, 1 submitter; last evaluated 2018-07-06). AlphaMissense: likely pathogenic (0.9876); Absent from gnomAD v4.1; Associated with syndromic X-linked intellectual disability Claes-Jensen type.

What condition is associated with KDM5C p.Val583Phe (c.1747G>T)?

KDM5C p.Val583Phe (c.1747G>T) is associated with syndromic X-linked intellectual disability Claes-Jensen type (ClinVar).

How common is KDM5C p.Val583Phe (c.1747G>T) in the general population?

KDM5C p.Val583Phe (c.1747G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KDM5C p.Val583Phe (c.1747G>T)?

AlphaMissense predicts likely pathogenic (score 0.9876) — an in-silico prediction, not a clinical call.

KDM5C p.Val583Phe

c.1747G>T · rs1602183890 · VCV691272

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9876 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

syndromic X-linked intellectual disability Claes-Jensen type

Computational evidence

Protein change
AlphaMissense	0.9876	likely pathogenic ✓ concordant with ClinVar
REVEL	0.853	moderately pathogenic-leaning
SaProt	LLR -14.01	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.28	acceptor gain · deltas
Pangolin	Δ0.26	gain · loss 0.08 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.6	GERP 2.8, phastCons 1
Regional constraint	o/e 0.20	constrained · MANE · 10 kb · p 1.4e-30 · regional, not allelic
Overall
CADD	25.0	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

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: KDM5C
Protein: p.Val583Phe
Coding: c.1747G>T
MANE Select: NM_004187
dbSNP: rs1602183890
Type: single nucleotide variant
Location: chrX:53201973 (GRCh38)
Structure: AlphaFold pLDDT 72.50 · 2 PDB
Residue 583: 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.Val583= Likely benign ★ same residue
KDM5C p.Arg332Ter Pathogenic ★★ same condition
KDM5C p.Arg599Cys Pathogenic/Likely 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

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-val583phe (accessed [today's date]).

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