Is KDM5C p.Asp87= (c.261C>T) pathogenic?

KDM5C p.Asp87= (c.261C>T) is classified Benign in KDM5C (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-29). Ultra-rare (popmax 0.0723%, amr); Associated with Spastic paraplegia.

What condition is associated with KDM5C p.Asp87= (c.261C>T)?

KDM5C p.Asp87= (c.261C>T) is associated with Spastic paraplegia (ClinVar).

How common is KDM5C p.Asp87= (c.261C>T) in the general population?

KDM5C p.Asp87= (c.261C>T) is ultra-rare (popmax 0.0723%, amr) (gnomAD).

KDM5C p.Asp87=

c.261C>T · rs781803586 · VCV2414557

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0723%, amr)

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 4.6	GERP -1, phastCons 1
Overall
CADD	9.004	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0723% Admixed American · 33/45,667 alleles

Filtering AF 0.0528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0462%

Overall 0.00314% 38/1,209,005 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0723%	1,384
Remaining individualsnot grpmax-eligible	0.0021%	47,576
European (non-Finnish)	0.000447%	223,672

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.Asp87=
Coding: c.261C>T
MANE Select: NM_004187
dbSNP: rs781803586
Type: single nucleotide variant
Location: chrX:53218366 (GRCh38)
Structure: AlphaFold pLDDT 72.50 · 2 PDB
Residue 87: the arid domain; a UniProt-annotated variant site (in mrxscj; no effect on subcellular location and enzymatic activity); an α-helix

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 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
KDM5C c.4038+6C>G Uncertain significance ★★ same condition
KDM5C p.Ala1085Ser Uncertain significance ★★ ⚠ same condition
KDM5C p.Ala1330Thr Uncertain significance ★★ ⚠ 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-asp87 (accessed [today's date]).

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