Is KDM5C p.Arg1007Cys (c.3019C>T) pathogenic?

KDM5C p.Arg1007Cys (c.3019C>T) is classified Uncertain significance in KDM5C (ClinVar, Single submitter, 1 submitter; last evaluated 2016-12-23). AlphaMissense: likely benign (0.1158); Ultra-rare (popmax 0.0114%, nfe).

How common is KDM5C p.Arg1007Cys (c.3019C>T) in the general population?

KDM5C p.Arg1007Cys (c.3019C>T) is ultra-rare (popmax 0.0114%, nfe) (gnomAD).

What do computational predictors say about KDM5C p.Arg1007Cys (c.3019C>T)?

AlphaMissense predicts likely benign (score 0.1158) — an in-silico prediction, not a clinical call.

KDM5C p.Arg1007Cys

c.3019C>T · rs781854324 · VCV391601

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1158 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0114%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1158	likely benign
REVEL	0.129	moderately benign-leaning
SaProt	LLR -8.39	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 0.6, phastCons 1
Regional constraint	o/e 0.41	unconstrained · MANE · 2,101 bp · p 3.1e-14 · regional, not allelic
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0114% European (non-Finnish) · 102/895,199 alleles

Filtering AF 0.00954% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00891%

Overall 0.00867% 105/1,210,749 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0114%	8,776
Remaining individualsnot grpmax-eligible	0.0042%	23,798
East Asian	0.00296%	33,798

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.Arg1007Cys
Coding: c.3019C>T
MANE Select: NM_004187
dbSNP: rs781854324
Type: single nucleotide variant
Location: chrX:53196017 (GRCh38)
Structure: AlphaFold pLDDT 72.50 · 2 PDB

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

Similar variants

KDM5C p.Arg1007His Conflicting classifications of pathogenicity ★ ⚠ same residue
KDM5C c.1243-2A>G Pathogenic/Likely pathogenic ★★ same type
KDM5C p.Arg332Ter Pathogenic ★★ same type
KDM5C p.Arg599Cys Pathogenic/Likely pathogenic ★★ same type
KDM5C p.Arg681Ter Pathogenic/Likely pathogenic ★★ same type
KDM5C p.Arg68Ter Pathogenic ★★ same type
KDM5C p.Arg750Trp Likely pathogenic ★★ same type
KDM5C p.Arg778Ter Pathogenic ★★ same type

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-arg1007cys (accessed [today's date]).

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