Is KCNC2 p.Phe388Ser (c.1163T>C) pathogenic?

KCNC2 p.Phe388Ser (c.1163T>C) is classified Pathogenic in KCNC2 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-06-28). AlphaMissense: likely pathogenic (0.9951); Absent from gnomAD v4.1; Associated with developmental and epileptic encephalopathy 103.

What condition is associated with KCNC2 p.Phe388Ser (c.1163T>C)?

KCNC2 p.Phe388Ser (c.1163T>C) is associated with developmental and epileptic encephalopathy 103 (ClinVar).

How common is KCNC2 p.Phe388Ser (c.1163T>C) in the general population?

KCNC2 p.Phe388Ser (c.1163T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KCNC2 p.Phe388Ser (c.1163T>C)?

AlphaMissense predicts likely pathogenic (score 0.9951) — an in-silico prediction, not a clinical call.

KCNC2 p.Phe388Ser

c.1163T>C · rs2547844200 · VCV2413122

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9951 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental and epileptic encephalopathy 103

Computational evidence

Protein change
AlphaMissense	0.9951	likely pathogenic ✓ concordant with ClinVar
REVEL	0.945	strongly pathogenic-leaning
SaProt	LLR -13.65	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 11	GERP 2.8, phastCons 1
Regional constraint	o/e 0.28	constrained · MANE · 593 bp · p 2e-28 · regional, not allelic
Overall
CADD	28.9	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: KCNC2
Protein: p.Phe388Ser
Coding: c.1163T>C
MANE Select: NM_139137
dbSNP: rs2547844200
Type: single nucleotide variant
Location: chr12:75050842 (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

developmental and epileptic encephalopathy 103 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KCNC2 p.Arg351Lys Pathogenic ★ same condition
KCNC2 p.Glu163Lys Likely pathogenic ★ same condition
KCNC2 p.Glu404Lys Likely pathogenic ★ same condition
KCNC2 p.Leu394Ser Likely pathogenic ★ same condition
KCNC2 p.Phe293Leu Likely pathogenic ★ same condition
KCNC2 p.Arg207Pro Uncertain significance ★ ⚠ same condition
KCNC2 p.Arg229Lys Uncertain significance ★ same condition
KCNC2 p.Asn116Ser 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-phe388ser (accessed [today's date]).

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