Is KCNT2 p.Ser805= (c.2415C>T) pathogenic?

KCNT2 p.Ser805= (c.2415C>T) is classified Likely benign in KCNT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-01). Very rare (popmax 0.0011%, sas).

How common is KCNT2 p.Ser805= (c.2415C>T) in the general population?

KCNT2 p.Ser805= (c.2415C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

KCNT2 p.Ser805=

c.2415C>T · rs748615136 · VCV3250869

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

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 -0.78	GERP -1
Overall
CADD	5.579	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/90,926 alleles

Overall 0.000124% 2/1,609,962 alleles · very rare exomes 2/1,458,116 · genomes 0/151,846 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	90,926
European (non-Finnish)	8.49e-05%	1,177,346

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.Ser805=
Coding: c.2415C>T
MANE Select: NM_198503
dbSNP: rs748615136
Type: single nucleotide variant
Location: chr1:196315960 (GRCh38)
Gene constraint: LOEUF 0.744 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.42
Residue 805: the rck n-terminal 2 domain

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

Similar variants

KCNT2 p.Ser805Gly Uncertain significance ★ same residue
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

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-ser805 (accessed [today's date]).

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