Is KCNC1 p.Pro461= (c.1383G>A) pathogenic?

KCNC1 p.Pro461= (c.1383G>A) is classified Likely benign in KCNC1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-03). Very rare (popmax 0.00517%, nfe); Associated with progressive myoclonic epilepsy type 7.

What condition is associated with KCNC1 p.Pro461= (c.1383G>A)?

KCNC1 p.Pro461= (c.1383G>A) is associated with progressive myoclonic epilepsy type 7 (ClinVar).

How common is KCNC1 p.Pro461= (c.1383G>A) in the general population?

KCNC1 p.Pro461= (c.1383G>A) is very rare (popmax 0.00517%, nfe) (gnomAD).

How is Progressive myoclonic epilepsy type 7 inherited?

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

KCNC1 p.Pro461=

c.1383G>A · rs200078349 · VCV1639774

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00517%, nfe)

Conditions

progressive myoclonic epilepsy type 7

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.5	GERP -4.1
Overall
CADD	5.07	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00517% European (non-Finnish) · 61/1,180,026 alleles

Filtering AF 0.0041% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00372%

Overall 0.00384% 62/1,614,184 alleles · very rare exomes 59/1,461,866 · genomes 3/152,318 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00517%	19,345
African / African-American	0.00133%	75,054

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: KCNC1
Protein: p.Pro461=
Coding: c.1383G>A
MANE Select: NM_001112741
dbSNP: rs200078349
Type: single nucleotide variant
Location: chr11:17772477 (GRCh38)
Gene constraint: LOEUF 0.363 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 79.51 · 10 PDB
Residue 461: an α-helix

Full KCNC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

progressive myoclonic epilepsy type 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Progressive myoclonic epilepsy type 7 (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood

Similar variants

KCNC1 p.Pro461Leu Uncertain significance ★ ⚠ same residue
KCNC1 p.Ala421Val Pathogenic/Likely pathogenic ★★ same condition
KCNC1 p.Arg320His Pathogenic/Likely pathogenic ★★ same condition
KCNC1 p.Thr399Met Pathogenic/Likely pathogenic ★★ same condition
KCNC1 p.Val425Met Pathogenic/Likely pathogenic ★★ same condition
KCNC1 p.Ala360Thr Uncertain significance ★★ ⚠ same condition
KCNC1 p.Ala418Ser Uncertain significance ★★ ⚠ same condition
KCNC1 p.Ala510Val 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/kcnc1-p-pro461 (accessed [today's date]).

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