Is KCNC3 p.Pro43Ser (c.127C>T) pathogenic?

KCNC3 p.Pro43Ser (c.127C>T) is classified Benign/Likely benign in KCNC3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-27). AlphaMissense: likely benign (0.0809); Rare (popmax 0.347%, afr); Associated with Inborn genetic diseases.

What condition is associated with KCNC3 p.Pro43Ser (c.127C>T)?

KCNC3 p.Pro43Ser (c.127C>T) is associated with Inborn genetic diseases (ClinVar).

How common is KCNC3 p.Pro43Ser (c.127C>T) in the general population?

KCNC3 p.Pro43Ser (c.127C>T) is rare (popmax 0.347%, afr) (gnomAD).

What do computational predictors say about KCNC3 p.Pro43Ser (c.127C>T)?

AlphaMissense predicts likely benign (score 0.0809) — an in-silico prediction, not a clinical call.

KCNC3 p.Pro43Ser

c.127C>T · rs928573902 · VCV447619

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0809 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.347%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0809	likely benign
REVEL	0.272	benign-leaning
SaProt	LLR -8.46	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -2.8, phastCons 1
Regional constraint	o/e 1.54	unconstrained · MANE · 204 bp · p 6.7e-07 · regional, not allelic
Overall
CADD	17.14	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

Grpmax group 0.347% African / African-American · 190/54,812 alleles

Filtering AF 0.306% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.291%

Overall 0.0245% 215/877,572 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.347%	288
Remaining individualsnot grpmax-eligible	0.0457%	2,189
Admixed American	0.0285%	3,512
European (non-Finnish)	0.000986%	101,380

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.Pro43Ser
Coding: c.127C>T
MANE Select: NM_004977
dbSNP: rs928573902
Type: single nucleotide variant
Location: chr19:50328956 (GRCh38)
Gene constraint: LOEUF 0.654 · pLI 0.30 (gnomAD)
Structure: AlphaFold pLDDT 66.01
Residue 43: 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.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-pro43ser (accessed [today's date]).

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