Is KCNC3 p.Ser571Pro (c.1711T>C) pathogenic?

KCNC3 p.Ser571Pro (c.1711T>C) is classified Uncertain significance in KCNC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-01). AlphaMissense: likely pathogenic (0.9454); Absent from gnomAD v4.1.

How common is KCNC3 p.Ser571Pro (c.1711T>C) in the general population?

KCNC3 p.Ser571Pro (c.1711T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KCNC3 p.Ser571Pro (c.1711T>C)?

AlphaMissense predicts likely pathogenic (score 0.9454) — an in-silico prediction, not a clinical call.

KCNC3 p.Ser571Pro

c.1711T>C · rs2513798922 · VCV2650324

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9454 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9454	likely pathogenic
REVEL	0.656	pathogenic-leaning
SaProt	LLR -7.27	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 11	GERP 2.1, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 3,038 bp · p 0.056 · regional, not allelic
Overall
CADD	25.4	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.Ser571Pro
Coding: c.1711T>C
MANE Select: NM_004977
dbSNP: rs2513798922
Type: single nucleotide variant
Location: chr19:50323242 (GRCh38)
Gene constraint: LOEUF 0.654 · pLI 0.30 (gnomAD)
Structure: AlphaFold pLDDT 66.01
Residue 571: the 'disordered' region

Full KCNC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KCNC3 p.Ser571Leu Uncertain significance ★★ ⚠ same residue
KCNC3 p.Ser571= Likely benign ★★ same residue
KCNC3 p.Arg420His Pathogenic ★★ same type
KCNC3 p.Arg423His Pathogenic ★★ same type
KCNC3 p.Ala295Thr Uncertain significance ★★ ⚠ same type
KCNC3 p.Ala44Ser Uncertain significance ★★ ⚠ same type
KCNC3 p.Ala615Val Uncertain significance ★★ ⚠ same type
KCNC3 p.Ala749Thr Uncertain significance ★★ ⚠ 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/kcnc3-p-ser571pro (accessed [today's date]).

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