Is KCNC3 p.Ser9Phe (c.26C>T) pathogenic?

KCNC3 p.Ser9Phe (c.26C>T) is classified Uncertain significance in KCNC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-16). AlphaMissense: likely benign (0.2251); Ultra-rare (popmax 0.0278%, mid); Associated with Inborn genetic diseases.

What condition is associated with KCNC3 p.Ser9Phe (c.26C>T)?

KCNC3 p.Ser9Phe (c.26C>T) is associated with Inborn genetic diseases (ClinVar).

How common is KCNC3 p.Ser9Phe (c.26C>T) in the general population?

KCNC3 p.Ser9Phe (c.26C>T) is ultra-rare (popmax 0.0278%, mid) (gnomAD).

What do computational predictors say about KCNC3 p.Ser9Phe (c.26C>T)?

AlphaMissense predicts likely benign (score 0.2251) — an in-silico prediction, not a clinical call.

KCNC3 p.Ser9Phe

c.26C>T · rs776349163 · VCV2485994

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2251 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0278%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2251	likely benign
REVEL	0.343	indeterminate
SaProt	LLR -6.81	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 6.6	GERP -2.2, phastCons 1
Regional constraint	o/e 1.54	unconstrained · MANE · 204 bp · p 6.7e-07 · regional, not allelic
Overall
CADD	23.8	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 0.0278% Middle Eastern · 1/3,598 alleles

Overall 8.42e-05% 1/1,187,926 alleles · ultra-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: KCNC3
Protein: p.Ser9Phe
Coding: c.26C>T
MANE Select: NM_004977
dbSNP: rs776349163
Type: single nucleotide variant
Location: chr19:50329057 (GRCh38)
Gene constraint: LOEUF 0.654 · pLI 0.30 (gnomAD)
Structure: AlphaFold pLDDT 66.01
Residue 9: the 'disordered' region; the 'important for normal n-type inactivation' region

Full KCNC3 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

KCNC3 p.Ser9Cys Uncertain significance ★ ⚠ same residue
KCNC3 p.Ala44Ser Uncertain significance ★★ ⚠ same condition
KCNC3 p.Arg417His Uncertain significance ★★ ⚠ same condition
KCNC3 p.Arg625Ser Uncertain significance ★★ ⚠ same condition
KCNC3 p.Asp221His Uncertain significance ★★ ⚠ same condition
KCNC3 p.Cys646Trp Uncertain significance ★★ ⚠ same condition
KCNC3 p.Gln39Pro Uncertain significance ★★ ⚠ same condition
KCNC3 p.Glu241Val 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/kcnc3-p-ser9phe (accessed [today's date]).

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