Is KCNN4 p.Ser367Phe (c.1100C>T) pathogenic?

KCNN4 p.Ser367Phe (c.1100C>T) is classified Uncertain significance in KCNN4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-31). AlphaMissense: ambiguous (0.5047); Absent from gnomAD v4.1; Associated with dehydrated hereditary stomatocytosis 2.

What condition is associated with KCNN4 p.Ser367Phe (c.1100C>T)?

KCNN4 p.Ser367Phe (c.1100C>T) is associated with dehydrated hereditary stomatocytosis 2 (ClinVar).

How common is KCNN4 p.Ser367Phe (c.1100C>T) in the general population?

KCNN4 p.Ser367Phe (c.1100C>T) is absent from gnomAD v4.1 (gnomAD).

How is Dehydrated hereditary stomatocytosis inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about KCNN4 p.Ser367Phe (c.1100C>T)?

AlphaMissense predicts ambiguous (score 0.5047) — an in-silico prediction, not a clinical call.

KCNN4 p.Ser367Phe

c.1100C>T · VCV4079072

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5047 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

dehydrated hereditary stomatocytosis 2

Computational evidence

Protein change
AlphaMissense	0.5047	ambiguous
REVEL	0.688	pathogenic-leaning
SaProt	LLR -11.04	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.3, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 1,997 bp · p 0.095 · regional, not allelic
Overall
CADD	31.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: KCNN4
Protein: p.Ser367Phe
Coding: c.1100C>T
MANE Select: NM_002250
Type: single nucleotide variant
Location: chr19:43768982 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.55 · 17 PDB
Residue 367: an α-helix

Full KCNN4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

dehydrated hereditary stomatocytosis 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Dehydrated hereditary stomatocytosis (Orphanet):

Inheritance: Autosomal dominant
Onset: Antenatal, Neonatal
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

KCNN4 p.Arg352His Pathogenic ★★ ⚠ same condition
KCNN4 p.Ala336Val Uncertain significance ★★ ⚠ same condition
KCNN4 p.Arg342His Uncertain significance ★★ ⚠ same condition
KCNN4 p.Arg97Ser Uncertain significance ★★ ⚠ same condition
KCNN4 p.Asn91Tyr Uncertain significance ★★ ⚠ same condition
KCNN4 p.Gly2Ser Uncertain significance ★★ ⚠ same condition
KCNN4 p.Ile76Met Uncertain significance ★★ ⚠ same condition
KCNN4 p.Leu12Phe 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/kcnn4-p-ser367phe (accessed [today's date]).

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