Is KDM5C p.Ala720= (c.2160C>T) pathogenic?

KDM5C p.Ala720= (c.2160C>T) is classified Likely benign in KDM5C (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-04). Very rare (popmax 0.00697%, afr); Associated with Spastic paraplegia.

What condition is associated with KDM5C p.Ala720= (c.2160C>T)?

KDM5C p.Ala720= (c.2160C>T) is associated with Spastic paraplegia (ClinVar).

How common is KDM5C p.Ala720= (c.2160C>T) in the general population?

KDM5C p.Ala720= (c.2160C>T) is very rare (popmax 0.00697%, afr) (gnomAD).

KDM5C p.Ala720=

c.2160C>T · rs369560779 · VCV1972722

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00697%, afr)

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	GERP 0.12, phastCons 1
Overall
CADD	9.928	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00697% African / African-American · 4/57,411 alleles

Filtering AF 0.00232% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00139%

Overall 0.000413% 5/1,210,710 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00697%	14,353
Admixed American	0.00218%	45,854

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.Ala720=
Coding: c.2160C>T
MANE Select: NM_004187
dbSNP: rs369560779
Type: single nucleotide variant
Location: chrX:53199060 (GRCh38)
Structure: AlphaFold pLDDT 72.50 · 2 PDB
Residue 720: a β-strand

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-ala720 (accessed [today's date]).

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