Is KDM5C p.Arg68fs (c.202dup) pathogenic?

KDM5C p.Arg68fs (c.202dup) is classified Pathogenic in KDM5C (ClinVar, Single submitter, 2 submitters; last evaluated 2022-02-07). Very rare (popmax 0.00176%, sas); Associated with syndromic X-linked intellectual disability Claes-Jensen type.

What condition is associated with KDM5C p.Arg68fs (c.202dup)?

KDM5C p.Arg68fs (c.202dup) is associated with syndromic X-linked intellectual disability Claes-Jensen type (ClinVar).

How common is KDM5C p.Arg68fs (c.202dup) in the general population?

KDM5C p.Arg68fs (c.202dup) is very rare (popmax 0.00176%, sas) (gnomAD).

KDM5C p.Arg68fs

c.202dup · rs782600511 · VCV9773

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00176%, sas)

Conditions

syndromic X-linked intellectual disability Claes-Jensen type

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 2 of 26
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00176% South Asian · 1/56,724 alleles

Overall 0.000898% 1/111,406 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.Arg68fs
Coding: c.202dup
MANE Select: NM_004187
dbSNP: rs782600511
Type: Duplication
Location: chrX:53220864 (GRCh38)
Structure: AlphaFold pLDDT 72.50 · 2 PDB

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.Arg68Ter Pathogenic ★★ same residue
KDM5C c.1746+4_1746+7dup Uncertain significance ★★ same condition
KDM5C c.2517-9_2517-7dup Benign/Likely benign ★★ same condition
KDM5C p.Arg1082fs Pathogenic ★ same condition
KDM5C p.Asn73fs Likely pathogenic ★ same condition
KDM5C p.Asp517fs Likely pathogenic ★ same condition
KDM5C p.Cys1047fs Likely pathogenic ★ same condition
KDM5C p.Gly626fs Likely 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-arg68fs (accessed [today's date]).

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