Is KCTD7 p.Arg99= (c.295C>A) pathogenic?

KCTD7 p.Arg99= (c.295C>A) is classified Likely benign in KCTD7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-22). Very rare (popmax 0.00223%, eas); Associated with progressive myoclonic epilepsy type 3.

What condition is associated with KCTD7 p.Arg99= (c.295C>A)?

KCTD7 p.Arg99= (c.295C>A) is associated with progressive myoclonic epilepsy type 3 (ClinVar).

How common is KCTD7 p.Arg99= (c.295C>A) in the general population?

KCTD7 p.Arg99= (c.295C>A) is very rare (popmax 0.00223%, eas) (gnomAD).

How is Progressive myoclonic epilepsy type 3 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

KCTD7 p.Arg99=

c.295C>A · rs267607199 · VCV2986728

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

progressive myoclonic epilepsy type 3

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 5.9	phastCons 1
Overall
CADD	12.85	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,882 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000434% 7/1,613,996 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,882
European (non-Finnish)	0.000508%	196,670

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: KCTD7
Protein: p.Arg99=
Coding: c.295C>A
MANE Select: NM_153033
dbSNP: rs267607199
Type: single nucleotide variant
Location: chr7:66633425 (GRCh38)
Gene constraint: LOEUF 0.902 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.67
Residue 99: the btb domain

Full KCTD7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

progressive myoclonic epilepsy type 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Progressive myoclonic epilepsy type 3 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy

Similar variants

KCTD7 p.Arg99Ter Pathogenic ★★ same residue
KCTD7 p.Arg99Leu Uncertain significance ★ ⚠ same residue
KCTD7 c.145-2A>G Likely pathogenic ★★ same condition
KCTD7 p.Ala174Thr Likely pathogenic ★★ ⚠ same condition
KCTD7 p.Arg184Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
KCTD7 p.Arg211Ter Pathogenic/Likely pathogenic ★★ same condition
KCTD7 p.Tyr276Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
KCTD7 c.144+3A>G 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/kctd7-p-arg99 (accessed [today's date]).

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