Is KDM5C p.Pro269= (c.807C>A) pathogenic?

KDM5C p.Pro269= (c.807C>A) is classified Likely benign in KDM5C (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-23). Very rare (popmax 0.00887%, eas); Associated with Spastic paraplegia.

What condition is associated with KDM5C p.Pro269= (c.807C>A)?

KDM5C p.Pro269= (c.807C>A) is associated with Spastic paraplegia (ClinVar).

How common is KDM5C p.Pro269= (c.807C>A) in the general population?

KDM5C p.Pro269= (c.807C>A) is very rare (popmax 0.00887%, eas) (gnomAD).

KDM5C p.Pro269=

c.807C>A · rs1415151995 · VCV2200885

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00887%, eas)

Conditions

Spastic paraplegia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.7	GERP -3.3
Overall
CADD	3.292	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00887% East Asian · 3/33,832 alleles

Filtering AF 0.00235% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00125%

Overall 0.000364% 4/1,097,901 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00887%	11,277
Admixed American	0.00217%	46,106

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.Pro269=
Coding: c.807C>A
MANE Select: NM_004187
dbSNP: rs1415151995
Type: single nucleotide variant
Location: chrX:53215951 (GRCh38)
Structure: AlphaFold pLDDT 72.50 · 2 PDB

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

Disease context

Spastic paraplegia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KDM5C p.Pro269Ala Uncertain significance ★★ ⚠ same residue
KDM5C p.Pro269Arg Uncertain significance ★ ⚠ same residue
KDM5C p.Pro269Leu Uncertain significance ★ ⚠ same residue
KDM5C c.1243-2A>G Pathogenic/Likely pathogenic ★★ same condition
KDM5C p.Arg681Ter Pathogenic/Likely pathogenic ★★ same condition
KDM5C p.Arg750Trp Likely pathogenic ★★ same condition
KDM5C p.Arg778Ter Pathogenic ★★ same condition
KDM5C p.Gln588Ter 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-pro269 (accessed [today's date]).

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