Is KCNC3 p.Pro334Ser (c.1000C>T) pathogenic?

KCNC3 p.Pro334Ser (c.1000C>T) is classified Uncertain significance in KCNC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-19). AlphaMissense: likely benign (0.1386); Absent from gnomAD v4.1.

How common is KCNC3 p.Pro334Ser (c.1000C>T) in the general population?

KCNC3 p.Pro334Ser (c.1000C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KCNC3 p.Pro334Ser (c.1000C>T)?

AlphaMissense predicts likely benign (score 0.1386) — an in-silico prediction, not a clinical call.

KCNC3 p.Pro334Ser

c.1000C>T · VCV3363229

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1386 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1386	likely benign
REVEL	0.253	benign-leaning
SaProt	LLR -10.19	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP -1.2, phastCons 1
Regional constraint	o/e 0.53	unconstrained · MANE · 4,754 bp · p 1.6e-15 · regional, not allelic
Overall
CADD	17.6	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: KCNC3
Protein: p.Pro334Ser
Coding: c.1000C>T
MANE Select: NM_004977
Type: single nucleotide variant
Location: chr19:50323953 (GRCh38)
Gene constraint: LOEUF 0.654 · pLI 0.30 (gnomAD)
Structure: AlphaFold pLDDT 66.01

Full KCNC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KCNC3 p.Pro334Leu Uncertain significance ★★ ⚠ same residue
KCNC3 p.Pro334= Likely benign same residue
KCNC3 p.Arg420His Pathogenic ★★ same type
KCNC3 p.Arg423His Pathogenic ★★ same type
KCNC3 p.Ala295Thr Uncertain significance ★★ ⚠ same type
KCNC3 p.Ala44Ser Uncertain significance ★★ ⚠ same type
KCNC3 p.Ala615Val Uncertain significance ★★ ⚠ same type
KCNC3 p.Ala749Thr Uncertain significance ★★ ⚠ same type

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/kcnc3-p-pro334ser (accessed [today's date]).

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