Is KCTD7 p.Phe110= (c.330C>T) pathogenic?

KCTD7 p.Phe110= (c.330C>T) is classified Likely benign in KCTD7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-15). Very rare (popmax 0.0011%, sas); Associated with progressive myoclonic epilepsy type 3.

What condition is associated with KCTD7 p.Phe110= (c.330C>T)?

KCTD7 p.Phe110= (c.330C>T) is associated with progressive myoclonic epilepsy type 3 (ClinVar).

How common is KCTD7 p.Phe110= (c.330C>T) in the general population?

KCTD7 p.Phe110= (c.330C>T) is very rare (popmax 0.0011%, 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.Phe110=

c.330C>T · rs748562227 · VCV2112557

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

progressive myoclonic epilepsy type 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.192	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.83	phastCons 1
Overall
CADD	14.24	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,076 alleles

Overall 6.19e-05% 1/1,614,212 alleles · very rare exomes 1/1,461,890 · genomes 0/152,322 · 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.Phe110=
Coding: c.330C>T
MANE Select: NM_153033
dbSNP: rs748562227
Type: single nucleotide variant
Location: chr7:66638268 (GRCh38)
Gene constraint: LOEUF 0.902 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.67
Residue 110: 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.Phe110Leu 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
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-phe110 (accessed [today's date]).

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