Is ALPK2 p.Ala809Ser (c.2425G>T) pathogenic?

ALPK2 p.Ala809Ser (c.2425G>T) is classified Uncertain significance in ALPK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-04). AlphaMissense: likely benign (0.1239); Absent from gnomAD v4.1.

How common is ALPK2 p.Ala809Ser (c.2425G>T) in the general population?

ALPK2 p.Ala809Ser (c.2425G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ALPK2 p.Ala809Ser (c.2425G>T)?

AlphaMissense predicts likely benign (score 0.1239) — an in-silico prediction, not a clinical call.

ALPK2 p.Ala809Ser

c.2425G>T · rs2051661831 · VCV1791085

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1239 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1239	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -5.86	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.04	GERP 1.3, phastCons 0.023
Regional constraint	o/e 0.91	unconstrained · MANE · 130 kb · p 6.4e-06 · regional, not allelic
Overall
CADD	13.78	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.

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: ALPK2
Protein: p.Ala809Ser
Coding: c.2425G>T
MANE Select: NM_052947
dbSNP: rs2051661831
Type: single nucleotide variant
Location: chr18:58537762 (GRCh38)
Gene constraint: LOEUF 0.862 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 40.99

Full ALPK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ALPK2 p.Thr2079Met Uncertain significance ★★ ⚠ same type
ALPK2 p.Arg1913Cys Benign/Likely benign ★★ same type
ALPK2 p.Asp390= Likely benign ★★ same type
ALPK2 p.Glu1525= Benign/Likely benign ★★ same type
ALPK2 p.Glu2056= Benign/Likely benign ★★ same type
ALPK2 p.Gly696= Likely benign ★★ same type
ALPK2 p.Ser163= Benign/Likely benign ★★ same type
ALPK2 p.Ala1001Glu 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/alpk2-p-ala809ser (accessed [today's date]).

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