Is KCNC3 p.Pro24Leu (c.71C>T) pathogenic?

KCNC3 p.Pro24Leu (c.71C>T) is classified Benign/Likely benign in KCNC3 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-27). AlphaMissense: likely benign (0.0866); Ultra-rare (popmax 0.0831%, eas); Associated with Inborn genetic diseases.

What condition is associated with KCNC3 p.Pro24Leu (c.71C>T)?

KCNC3 p.Pro24Leu (c.71C>T) is associated with Inborn genetic diseases (ClinVar).

How common is KCNC3 p.Pro24Leu (c.71C>T) in the general population?

KCNC3 p.Pro24Leu (c.71C>T) is ultra-rare (popmax 0.0831%, eas) (gnomAD).

What do computational predictors say about KCNC3 p.Pro24Leu (c.71C>T)?

AlphaMissense predicts likely benign (score 0.0866) — an in-silico prediction, not a clinical call.

KCNC3 p.Pro24Leu

c.71C>T · rs775818633 · VCV718964

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0866 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0831%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0866	likely benign
REVEL	0.308	indeterminate
SaProt	LLR -8.99	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 3.3	GERP -1, phastCons 1
Regional constraint	o/e 1.54	unconstrained · MANE · 204 bp · p 6.7e-07 · regional, not allelic
Overall
CADD	20.5	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 0.0831% East Asian · 26/31,282 alleles

Filtering AF 0.0582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0498%

Overall 0.124% 1,610/1,301,918 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	3.7%	27
Remaining individualsnot grpmax-eligible	0.117%	853
East Asiangrpmax	0.0831%	1,203
European (non-Finnish)	0.0231%	4,323
South Asian	0.0184%	5,425

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro24Leu
Coding: c.71C>T
MANE Select: NM_004977
dbSNP: rs775818633
Type: single nucleotide variant
Location: chr19:50329012 (GRCh38)
Gene constraint: LOEUF 0.654 · pLI 0.30 (gnomAD)
Structure: AlphaFold pLDDT 66.01
Residue 24: 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-pro24leu (accessed [today's date]).

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