Is KCTD7 p.Val52Phe (c.154G>T) pathogenic?

KCTD7 p.Val52Phe (c.154G>T) is classified Uncertain significance in KCTD7 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-18). AlphaMissense: likely pathogenic (0.8901); Absent from gnomAD v4.1; Associated with progressive myoclonic epilepsy type 3.

What condition is associated with KCTD7 p.Val52Phe (c.154G>T)?

KCTD7 p.Val52Phe (c.154G>T) is associated with progressive myoclonic epilepsy type 3 (ClinVar).

How common is KCTD7 p.Val52Phe (c.154G>T) in the general population?

KCTD7 p.Val52Phe (c.154G>T) is absent from gnomAD v4.1 (gnomAD).

How is Progressive myoclonic epilepsy type 3 inherited?

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

What do computational predictors say about KCTD7 p.Val52Phe (c.154G>T)?

AlphaMissense predicts likely pathogenic (score 0.8901) — an in-silico prediction, not a clinical call.

KCTD7 p.Val52Phe

c.154G>T · rs2116763711 · VCV1470709

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8901 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

progressive myoclonic epilepsy type 3

Computational evidence

Protein change
AlphaMissense	0.8901	likely pathogenic
REVEL	0.504	indeterminate
SaProt	LLR -9.81	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 10 kb · p 5.6e-07 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: KCTD7
Protein: p.Val52Phe
Coding: c.154G>T
MANE Select: NM_153033
dbSNP: rs2116763711
Type: single nucleotide variant
Location: chr7:66633284 (GRCh38)
Gene constraint: LOEUF 0.902 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.67
Residue 52: 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 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
KCTD7 p.Ala124Gly 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-val52phe (accessed [today's date]).

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