Is ATP8A2 p.Ala44fs (c.130_131del) pathogenic?

ATP8A2 p.Ala44fs (c.130131del) is classified Conflicting classifications of pathogenicity in ATP8A2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-05-21). Very rare (popmax 0.00322%, nfe).

How common is ATP8A2 p.Ala44fs (c.130_131del) in the general population?

ATP8A2 p.Ala44fs (c.130_131del) is very rare (popmax 0.00322%, nfe) (gnomAD).

ATP8A2 p.Ala44fs

c.130_131del · rs774959381 · VCV1702569

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00322%, 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 2 of 37
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.7	GERP 1.2, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00322% European (non-Finnish) · 38/1,179,920 alleles

Filtering AF 0.00239% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0021%

Overall 0.00242% 39/1,613,942 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00322%	31,051
Remaining individualsnot grpmax-eligible	0.0016%	62,474

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.Ala44fs
Coding: c.130_131del
MANE Select: NM_016529
dbSNP: rs774959381
Type: Deletion
Location: chr13:25469030 (GRCh38)
Gene constraint: LOEUF 0.728 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 81.12

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.Asn596fs 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

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-ala44fs (accessed [today's date]).

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