Is ALPK2 p.Ser442= (c.1326A>C) pathogenic?

ALPK2 p.Ser442= (c.1326A>C) is classified Benign in ALPK2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-20). Common (popmax 7.54%, eas) — too common for a highly-penetrant pathogenic allele; Associated with ALPK2-related disorder.

What condition is associated with ALPK2 p.Ser442= (c.1326A>C)?

ALPK2 p.Ser442= (c.1326A>C) is associated with ALPK2-related disorder (ClinVar).

ALPK2 p.Ser442=

Q: How common is ALPK2 p.Ser442= (c.1326A>C) in the general population?

ALPK2 p.Ser442= (c.1326A>C) is common (popmax 7.54%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1326A>C · rs114432784 · VCV3059386

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 7.54%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

ALPK2-related disorder

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 -6.8	GERP -4.8
Overall
CADD	1.128	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.54% East Asian · 3,383/44,890 alleles

Filtering AF 7.32% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.24%

Overall 1.11% 17,953/1,614,178 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	7.54%	13
Admixed American	2.57%	39
Middle Eastern	2.51%	40
South Asian	2.45%	41
African / African-American	2.25%	44
Remaining individualsnot grpmax-eligible	1.68%	60
European (non-Finnish)	0.626%	160
Finnishnot grpmax-eligible	0.617%	162
Ashkenazi Jewishnot grpmax-eligible	0.402%	249

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: ALPK2
Protein: p.Ser442=
Coding: c.1326A>C
MANE Select: NM_052947
dbSNP: rs114432784
Type: single nucleotide variant
Location: chr18:58579450 (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

Disease context

ALPK2-related disorder

Similar variants

ALPK2 c.5353+7T>C Benign same condition
ALPK2 c.5501+4C>T Benign same condition
ALPK2 c.5501+5G>A Likely benign same condition
ALPK2 c.5501+7T>C Likely benign same condition
ALPK2 c.*7T>C Benign same condition
ALPK2 p.Ala1479= Benign same condition
ALPK2 p.Ala1551Ser Benign same condition
ALPK2 p.Ala1650Val Benign 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/alpk2-p-ser442 (accessed [today's date]).

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