Is KCNC3 p.Gln39Pro (c.116A>C) pathogenic?

KCNC3 p.Gln39Pro (c.116A>C) is classified Uncertain significance in KCNC3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-14). AlphaMissense: likely benign (0.0486); Ultra-rare (popmax 0.0155%, amr); Associated with Inborn genetic diseases.

What condition is associated with KCNC3 p.Gln39Pro (c.116A>C)?

KCNC3 p.Gln39Pro (c.116A>C) is associated with Inborn genetic diseases (ClinVar).

How common is KCNC3 p.Gln39Pro (c.116A>C) in the general population?

KCNC3 p.Gln39Pro (c.116A>C) is ultra-rare (popmax 0.0155%, amr) (gnomAD).

What do computational predictors say about KCNC3 p.Gln39Pro (c.116A>C)?

AlphaMissense predicts likely benign (score 0.0486) — an in-silico prediction, not a clinical call.

KCNC3 p.Gln39Pro

c.116A>C · rs1403069648 · VCV2903203

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0486 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0155%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0486	likely benign
REVEL	0.305	indeterminate
SaProt	LLR -5.01	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 -2.8	GERP -2.9
Regional constraint	o/e 1.54	unconstrained · MANE · 204 bp · p 6.7e-07 · regional, not allelic
Overall
CADD	10.05	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 0.0155% Admixed American · 3/19,328 alleles

Filtering AF 0.00572% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00409%

Overall 0.00144% 14/970,898 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0155%	6,443
African / African-American	0.0124%	8,090
Remaining individualsnot grpmax-eligible	0.00599%	16,697
European (non-Finnish)	0.000258%	387,490

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.Gln39Pro
Coding: c.116A>C
MANE Select: NM_004977
dbSNP: rs1403069648
Type: single nucleotide variant
Location: chr19:50328967 (GRCh38)
Gene constraint: LOEUF 0.654 · pLI 0.30 (gnomAD)
Structure: AlphaFold pLDDT 66.01
Residue 39: 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.Glu241Val Uncertain significance ★★ ⚠ same condition
KCNC3 p.Gly234Cys Uncertain significance ★★ ⚠ same condition
KCNC3 p.Gly237Arg 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-gln39pro (accessed [today's date]).

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