Is KCNT1 p.Val271Phe (c.811G>T) pathogenic?

KCNT1 p.Val271Phe (c.811G>T) is classified Pathogenic in KCNT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-06-01). AlphaMissense: ambiguous (0.415); Absent from gnomAD v4.1.

How common is KCNT1 p.Val271Phe (c.811G>T) in the general population?

KCNT1 p.Val271Phe (c.811G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KCNT1 p.Val271Phe (c.811G>T)?

AlphaMissense predicts ambiguous (score 0.415) — an in-silico prediction, not a clinical call.

KCNT1 p.Val271Phe

c.811G>T · rs1831669014 · VCV871329

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.415 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,764)

Computational evidence

Protein change
AlphaMissense	0.415	ambiguous
REVEL	0.508	indeterminate
SaProt	LLR -7.37	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 20 kb · p 2.2e-17 · regional, not allelic
Overall
CADD	28.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V252F vs ClinVar V271F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,613,764). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: KCNT1
Protein: p.Val271Phe
Coding: c.811G>T
MANE Select: NM_020822
dbSNP: rs1831669014
Type: single nucleotide variant
Location: chr9:135758465 (GRCh38)
Gene constraint: LOEUF 0.682 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.94 · 6 PDB
Residue 271: an α-helix

Full KCNT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KCNT1 p.Val271Ile Uncertain significance ★ ⚠ same residue
KCNT1 p.Ala477Thr Pathogenic/Likely pathogenic ★★ same type
KCNT1 p.Ala934Ser Pathogenic/Likely pathogenic ★★ same type
KCNT1 p.Ala934Thr Pathogenic ★★ same type
KCNT1 p.Ala966Thr Pathogenic/Likely pathogenic ★★ same type
KCNT1 p.Arg262Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
KCNT1 p.Arg356Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
KCNT1 p.Arg398Gln Pathogenic/Likely pathogenic ★★ ⚠ 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/kcnt1-p-val271phe (accessed [today's date]).

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