Is KCNC3 p.Arg125= (c.375C>T) pathogenic?

KCNC3 p.Arg125= (c.375C>T) is classified Likely benign in KCNC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-01). Very rare (popmax 0.00112%, sas).

How common is KCNC3 p.Arg125= (c.375C>T) in the general population?

KCNC3 p.Arg125= (c.375C>T) is very rare (popmax 0.00112%, sas) (gnomAD).

KCNC3 p.Arg125=

c.375C>T · VCV3777984

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00112%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP -1.9, phastCons 1
Overall
CADD	13.27	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00112% South Asian · 1/89,664 alleles

Overall 6.91e-05% 1/1,448,030 alleles · very 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.Arg125=
Coding: c.375C>T
MANE Select: NM_004977
Type: single nucleotide variant
Location: chr19:50328708 (GRCh38)
Gene constraint: LOEUF 0.654 · pLI 0.30 (gnomAD)
Structure: AlphaFold pLDDT 66.01

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

Similar variants

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
KCNC3 p.Arg417His Uncertain significance ★★ ⚠ same type
KCNC3 p.Arg625Ser 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-arg125 (accessed [today's date]).

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