Is KCNC3 p.Phe708Cys (c.2123T>G) pathogenic?

KCNC3 p.Phe708Cys (c.2123T>G) is classified Uncertain significance in KCNC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-13). AlphaMissense: likely pathogenic (0.9671); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with KCNC3 p.Phe708Cys (c.2123T>G)?

KCNC3 p.Phe708Cys (c.2123T>G) is associated with Inborn genetic diseases (ClinVar).

How common is KCNC3 p.Phe708Cys (c.2123T>G) in the general population?

KCNC3 p.Phe708Cys (c.2123T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KCNC3 p.Phe708Cys (c.2123T>G)?

AlphaMissense predicts likely pathogenic (score 0.9671) — an in-silico prediction, not a clinical call.

KCNC3 p.Phe708Cys

c.2123T>G · rs2513795987 · VCV3113114

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9671 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9671	likely pathogenic
REVEL	0.764	pathogenic-leaning
SaProt	LLR -6.58	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.6, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 3,038 bp · p 0.056 · regional, not allelic
Overall
CADD	24.7	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: KCNC3
Protein: p.Phe708Cys
Coding: c.2123T>G
MANE Select: NM_004977
dbSNP: rs2513795987
Type: single nucleotide variant
Location: chr19:50320640 (GRCh38)
Gene constraint: LOEUF 0.654 · pLI 0.30 (gnomAD)
Structure: AlphaFold pLDDT 66.01
Residue 708: the 'disordered' 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.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
KCNC3 p.Gly234Cys 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-phe708cys (accessed [today's date]).

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