Is KCNC2 p.Pro201Arg (c.602C>G) pathogenic?

KCNC2 p.Pro201Arg (c.602C>G) is classified Uncertain significance in KCNC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-29). AlphaMissense: likely benign (0.0809); Very rare (popmax 0.000687%, nfe); Associated with Inborn genetic diseases.

What condition is associated with KCNC2 p.Pro201Arg (c.602C>G)?

KCNC2 p.Pro201Arg (c.602C>G) is associated with Inborn genetic diseases (ClinVar).

How common is KCNC2 p.Pro201Arg (c.602C>G) in the general population?

KCNC2 p.Pro201Arg (c.602C>G) is very rare (popmax 0.000687%, nfe) (gnomAD).

What do computational predictors say about KCNC2 p.Pro201Arg (c.602C>G)?

AlphaMissense predicts likely benign (score 0.0809) — an in-silico prediction, not a clinical call.

KCNC2 p.Pro201Arg

c.602C>G · VCV4041446

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0809 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000687%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0809	likely benign
REVEL	0.37	indeterminate
SaProt	LLR -6.97	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.3, phastCons 1
Regional constraint	o/e 1.32	unconstrained · MANE · 142 bp · p 0.0057 · regional, not allelic
Overall
CADD	21.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.000687% European (non-Finnish) · 8/1,165,100 alleles

Filtering AF 0.000295% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000214%

Overall 0.00056% 8/1,428,908 alleles · very rare

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: KCNC2
Protein: p.Pro201Arg
Coding: c.602C>G
MANE Select: NM_139137
Type: single nucleotide variant
Location: chr12:75207382 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KCNC2 p.Ala187Thr Uncertain significance ★★ ⚠ same condition
KCNC2 c.*731A>T Uncertain significance ★ same condition
KCNC2 c.*764C>T Uncertain significance ★ same condition
KCNC2 c.*773A>G Uncertain significance ★ same condition
KCNC2 c.*779G>A Uncertain significance ★ same condition
KCNC2 p.Ala196Thr Uncertain significance ★ ⚠ same condition
KCNC2 p.Ala516Ser Uncertain significance ★ ⚠ same condition
KCNC2 p.Ala92Ser 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/kcnc2-p-pro201arg (accessed [today's date]).

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