Is ATP8A2 p.Asn596fs (c.1787del) pathogenic?

ATP8A2 p.Asn596fs (c.1787del) is classified Pathogenic in ATP8A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-12-27). Very rare (popmax 8.89e-05%, nfe).

How common is ATP8A2 p.Asn596fs (c.1787del) in the general population?

ATP8A2 p.Asn596fs (c.1787del) is very rare (popmax 8.89e-05%, nfe) (gnomAD).

ATP8A2 p.Asn596fs

c.1787del · rs1064795308 · VCV421706

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.89e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 21 of 37
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.5	GERP -2.4, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.89e-05% European (non-Finnish) · 1/1,125,182 alleles

Overall 7.13e-05% 1/1,401,582 alleles · very rare

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: ATP8A2
Protein: p.Asn596fs
Coding: c.1787del
MANE Select: NM_016529
dbSNP: rs1064795308
Type: Deletion
Location: chr13:25578818 (GRCh38)
Gene constraint: LOEUF 0.728 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 81.12
Residue 596: a UniProt-annotated variant site (in camrq4; uncertain significance)

Full ATP8A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATP8A2 c.1474-2del Likely pathogenic ★ same type
ATP8A2 c.321+3_321+8del Likely pathogenic ★ same type
ATP8A2 p.Asn886fs Pathogenic ★ same type
ATP8A2 p.Asp70fs Likely pathogenic ★ same type
ATP8A2 p.Gly173fs Likely pathogenic ★ same type
ATP8A2 p.Leu231fs Pathogenic ★ same type
ATP8A2 p.Leu660fs Likely pathogenic ★ same type
ATP8A2 p.Pro495fs 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/atp8a2-p-asn596fs (accessed [today's date]).

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