Is KDM5C p.Lys188= (c.564G>A) pathogenic?

KDM5C p.Lys188= (c.564G>A) is classified Benign/Likely benign in KDM5C (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-03). Low-frequency (popmax 1.91%, sas); Associated with Inborn genetic diseases.

What condition is associated with KDM5C p.Lys188= (c.564G>A)?

KDM5C p.Lys188= (c.564G>A) is associated with Inborn genetic diseases, syndromic X-linked intellectual disability Claes-Jensen type (ClinVar).

How common is KDM5C p.Lys188= (c.564G>A) in the general population?

KDM5C p.Lys188= (c.564G>A) is low-frequency (popmax 1.91%, sas) (gnomAD).

KDM5C p.Lys188=

c.564G>A · rs61751437 · VCV94882

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.91%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.22	GERP -2.3, phastCons 0.27
Overall
CADD	7.063	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.91% South Asian · 1,083/56,631 alleles

Filtering AF 1.82% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.78%

Overall 1.5% 18,196/1,209,118 alleles · low-frequency exomes 16,987/1,097,479 · genomes 1,209/111,639 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	2.52%	40
South Asiangrpmax	1.91%	52
European (non-Finnish)	1.64%	61
Remaining individualsnot grpmax-eligible	1.31%	76
Ashkenazi Jewishnot grpmax-eligible	1.31%	76
Middle Eastern	0.645%	155
Admixed American	0.496%	202
African / African-American	0.154%	649

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Lys188=
Coding: c.564G>A
MANE Select: NM_004187
dbSNP: rs61751437
Type: single nucleotide variant
Location: chrX:53217236 (GRCh38)
Structure: AlphaFold pLDDT 72.50 · 2 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: syndromic X-linked intellectual disability Claes-Jensen type

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.Arg68Ter 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-lys188 (accessed [today's date]).

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