Is KDM5C p.Pro412= (c.1236C>T) pathogenic?

KDM5C p.Pro412= (c.1236C>T) is classified Benign/Likely benign in KDM5C (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-28). Rare (popmax 0.897%, afr); Associated with syndromic X-linked intellectual disability Claes-Jensen type.

What condition is associated with KDM5C p.Pro412= (c.1236C>T)?

KDM5C p.Pro412= (c.1236C>T) is associated with syndromic X-linked intellectual disability Claes-Jensen type (ClinVar).

How common is KDM5C p.Pro412= (c.1236C>T) in the general population?

KDM5C p.Pro412= (c.1236C>T) is rare (popmax 0.897%, afr) (gnomAD).

KDM5C p.Pro412=

c.1236C>T · rs147546892 · VCV129373

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.897%, afr)

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.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.41 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.2	GERP -4.5
Overall
CADD	1.874	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.897% African / African-American · 514/57,280 alleles

Filtering AF 0.833% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.808%

Overall 0.051% 617/1,209,571 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.897%	111
Middle Eastern	0.161%	622
Remaining individualsnot grpmax-eligible	0.0778%	1,286
Admixed American	0.0633%	1,579
South Asian	0.00353%	28,358
European (non-Finnish)	0.00313%	31,955

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.Pro412=
Coding: c.1236C>T
MANE Select: NM_004187
dbSNP: rs147546892
Type: single nucleotide variant
Location: chrX:53211793 (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.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
KDM5C p.Gln199Ter 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-pro412 (accessed [today's date]).

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