Is KCNC2 p.Arg348Ser (c.1044G>T) pathogenic?

KCNC2 p.Arg348Ser (c.1044G>T) is classified Uncertain significance in KCNC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-08). AlphaMissense: likely pathogenic (0.9977); Absent from gnomAD v4.1.

How common is KCNC2 p.Arg348Ser (c.1044G>T) in the general population?

KCNC2 p.Arg348Ser (c.1044G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KCNC2 p.Arg348Ser (c.1044G>T)?

AlphaMissense predicts likely pathogenic (score 0.9977) — an in-silico prediction, not a clinical call.

KCNC2 p.Arg348Ser

c.1044G>T · VCV3603172

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9977 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9977	likely pathogenic
REVEL	0.825	moderately pathogenic-leaning
SaProt	LLR -15.64	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP 1.1, phastCons 1
Regional constraint	o/e 0.28	constrained · MANE · 593 bp · p 2e-28 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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: KCNC2
Protein: p.Arg348Ser
Coding: c.1044G>T
MANE Select: NM_139137
Type: single nucleotide variant
Location: chr12:75050961 (GRCh38)
Gene constraint: LOEUF 0.666 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 68.26

Full KCNC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KCNC2 p.Ala187Thr Uncertain significance ★★ ⚠ same type
KCNC2 p.Ala431Val Uncertain significance ★★ ⚠ same type
KCNC2 p.Cys509Phe Uncertain significance ★★ ⚠ same type
KCNC2 p.Phe382= Benign/Likely benign ★★ same type
KCNC2 p.Arg351Lys Pathogenic ★ same type
KCNC2 p.Glu163Lys Likely pathogenic ★ same type
KCNC2 p.Glu404Lys Likely pathogenic ★ same type
KCNC2 p.Leu394Ser Likely pathogenic ★ 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/kcnc2-p-arg348ser (accessed [today's date]).

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