Is KCNN2 p.Ser770Pro (c.2308T>C) pathogenic?

KCNN2 p.Ser770Pro (c.2308T>C) is classified Uncertain significance in KCNN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-13). AlphaMissense: likely benign (0.1183); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with KCNN2 p.Ser770Pro (c.2308T>C)?

KCNN2 p.Ser770Pro (c.2308T>C) is associated with Inborn genetic diseases (ClinVar).

How common is KCNN2 p.Ser770Pro (c.2308T>C) in the general population?

KCNN2 p.Ser770Pro (c.2308T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KCNN2 p.Ser770Pro (c.2308T>C)?

AlphaMissense predicts likely benign (score 0.1183) — an in-silico prediction, not a clinical call.

KCNN2 p.Ser770Pro

c.2308T>C · rs377469782 · VCV2536800

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1183 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1183	likely benign
REVEL	0.579	indeterminate
SaProt	LLR -6.37	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 2.3, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 9,022 bp · p 0.55 · regional, not allelic
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S558P vs ClinVar S770P) — verify the residue.

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: KCNN2
Protein: p.Ser770Pro
Coding: c.2308T>C
MANE Select: NM_021614
dbSNP: rs377469782
Type: single nucleotide variant
Location: chr5:114496114 (GRCh38)
Gene constraint: LOEUF 0.661 · pLI 0.07 (gnomAD)
Structure: AlphaFold pLDDT 77.98 · 16 PDB
Residue 558 UniProt numbering: the 'disordered' region; a UniProt-annotated variant site (in nedmab)

Full KCNN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KCNN2 p.Arg233Leu Uncertain significance ★★ ⚠ same condition
KCNN2 p.Ile730Val Uncertain significance ★★ ⚠ same condition
KCNN2 p.Ile744Met Uncertain significance ★★ ⚠ same condition
KCNN2 p.Lys332Arg Uncertain significance ★★ ⚠ same condition
KCNN2 p.Pro248Leu Uncertain significance ★★ ⚠ same condition
KCNN2 p.Ser281Phe Uncertain significance ★★ ⚠ same condition
KCNN2 p.Ser788Pro Uncertain significance ★★ ⚠ same condition
KCNN2 p.Ala258Val 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/kcnn2-p-ser770pro (accessed [today's date]).

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