Is KCTD7 p.Pro201= (c.603C>G) pathogenic?

KCTD7 p.Pro201= (c.603C>G) is classified Likely benign in KCTD7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-05). Ultra-rare (popmax 0.0121%, sas); Associated with progressive myoclonic epilepsy type 3.

What condition is associated with KCTD7 p.Pro201= (c.603C>G)?

KCTD7 p.Pro201= (c.603C>G) is associated with progressive myoclonic epilepsy type 3 (ClinVar).

How common is KCTD7 p.Pro201= (c.603C>G) in the general population?

KCTD7 p.Pro201= (c.603C>G) is ultra-rare (popmax 0.0121%, sas) (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.Pro201=

c.603C>G · VCV4738524

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0121%, sas)

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 0.23	phastCons 0.97
Overall
CADD	8.274	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0121% South Asian · 11/91,092 alleles

Filtering AF 0.00676% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00522%

Overall 0.000681% 11/1,614,214 alleles · ultra-rare exomes 11/1,461,888 · genomes 0/152,326 · joint denominator

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.Pro201=
Coding: c.603C>G
MANE Select: NM_153033
Type: single nucleotide variant
Location: chr7:66638965 (GRCh38)
Gene constraint: LOEUF 0.902 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.67

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.Pro201Arg Uncertain significance ★ ⚠ same residue
KCTD7 p.Pro201His Uncertain significance ★ ⚠ same residue
KCTD7 p.Pro201Thr 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.Arg99Ter 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/kctd7-p-pro201 (accessed [today's date]).

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