Is KCNT2 p.Ser485= (c.1455C>T) pathogenic?

KCNT2 p.Ser485= (c.1455C>T) is classified Likely benign in KCNT2 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-09-16). Ultra-rare (popmax 0.0165%, mid).

How common is KCNT2 p.Ser485= (c.1455C>T) in the general population?

KCNT2 p.Ser485= (c.1455C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

KCNT2 p.Ser485=

c.1455C>T · rs141251248 · VCV3036516

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, 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 -1.9	GERP -3
Overall
CADD	9.947	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,078 alleles

Filtering AF 0.00462% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00423%

Overall 0.00608% 98/1,611,206 alleles · ultra-rare exomes 82/1,459,554 · genomes 16/151,652 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0313%	3,195
Middle Easterngrpmax	0.0165%	6,078
European (non-Finnish)	0.00577%	17,336
African / African-American	0.00402%	24,882
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,566
East Asian	0.00223%	44,752
South Asian	0.00221%	45,293
Admixed American	0.00168%	59,520
Remaining individualsnot grpmax-eligible	0.0016%	62,370

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: KCNT2
Protein: p.Ser485=
Coding: c.1455C>T
MANE Select: NM_198503
dbSNP: rs141251248
Type: single nucleotide variant
Location: chr1:196342177 (GRCh38)
Gene constraint: LOEUF 0.744 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.42

Full KCNT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KCNT2 p.Ala609Val Uncertain significance ★★ ⚠ same type
KCNT2 p.Ala711Val Uncertain significance ★★ ⚠ same type
KCNT2 p.Arg879Gln Uncertain significance ★★ ⚠ same type
KCNT2 p.Asn29Lys Uncertain significance ★★ ⚠ same type
KCNT2 p.Cys484Phe Uncertain significance ★★ ⚠ same type
KCNT2 p.Leu116Val Uncertain significance ★★ ⚠ same type
KCNT2 p.Leu536Pro Uncertain significance ★★ ⚠ same type
KCNT2 p.Met807Val 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/kcnt2-p-ser485 (accessed [today's date]).

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