Is KCNC2 p.Pro213Ser (c.637C>T) pathogenic?

KCNC2 p.Pro213Ser (c.637C>T) is classified Uncertain significance in KCNC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-31). AlphaMissense: ambiguous (0.4538); No allele count reported in gnomAD v4.1 (AN 1,576,202).

How common is KCNC2 p.Pro213Ser (c.637C>T) in the general population?

KCNC2 p.Pro213Ser (c.637C>T) is no allele count reported in gnomAD v4.1 (AN 1,576,202) (gnomAD).

What do computational predictors say about KCNC2 p.Pro213Ser (c.637C>T)?

AlphaMissense predicts ambiguous (score 0.4538) — an in-silico prediction, not a clinical call.

KCNC2 p.Pro213Ser

c.637C>T · rs2548167149 · VCV2442599

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4538 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,576,202)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4538	ambiguous
REVEL	0.671	pathogenic-leaning
SaProt	LLR -10.94	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	GERP 2.1, phastCons 1
Regional constraint	o/e 1.32	unconstrained · MANE · 142 bp · p 0.0057 · regional, not allelic
Overall
CADD	25.0	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

No allele count reported in gnomAD v4.1 (AN 1,576,202). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: KCNC2
Protein: p.Pro213Ser
Coding: c.637C>T
MANE Select: NM_139137
dbSNP: rs2548167149
Type: single nucleotide variant
Location: chr12:75207347 (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-pro213ser (accessed [today's date]).

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