Is KCNC3 p.Ser515= (c.1545G>A) pathogenic?

KCNC3 p.Ser515= (c.1545G>A) is classified Benign in KCNC3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-10). Rare (popmax 0.197%, mid).

How common is KCNC3 p.Ser515= (c.1545G>A) in the general population?

KCNC3 p.Ser515= (c.1545G>A) is rare (popmax 0.197%, mid) (gnomAD).

KCNC3 p.Ser515=

c.1545G>A · rs201156826 · VCV1665670

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.197%, mid)

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 -3.5	GERP -4.3
Overall
CADD	5.911	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.197% Middle Eastern · 12/6,084 alleles

Filtering AF 0.114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0892%

Overall 0.0116% 187/1,614,108 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.216%	463
Middle Easterngrpmax	0.197%	507
Remaining individualsnot grpmax-eligible	0.0288%	3,471
Admixed American	0.0233%	4,287
European (non-Finnish)	0.0061%	16,390
South Asian	0.00549%	18,219
East Asian	0.00223%	44,892
African / African-American	0.00133%	74,954

Ashkenazi Jewish 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.Ser515=
Coding: c.1545G>A
MANE Select: NM_004977
dbSNP: rs201156826
Type: single nucleotide variant
Location: chr19:50323408 (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-ser515 (accessed [today's date]).

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