Is ATP8A2 p.Arg142Ter (c.424C>T) pathogenic?

ATP8A2 p.Arg142Ter (c.424C>T) is classified Likely pathogenic in ATP8A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-09-14). Very rare (popmax 8.49e-05%, nfe).

How common is ATP8A2 p.Arg142Ter (c.424C>T) in the general population?

ATP8A2 p.Arg142Ter (c.424C>T) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

ATP8A2 p.Arg142Ter

c.424C>T · rs1064795610 · VCV422182

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 37
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.9, phastCons 1
Overall
CADD	38.0	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 8.49e-05% European (non-Finnish) · 1/1,177,528 alleles

Overall 0.000137% 2/1,455,540 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,498
European (non-Finnish)grpmax	8.49e-05%	1,177,528

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg142Ter
Coding: c.424C>T
MANE Select: NM_016529
dbSNP: rs1064795610
Type: single nucleotide variant
Location: chr13:25532275 (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.1782+2T>C Pathogenic ★★ same type
ATP8A2 c.2212-1G>C Pathogenic ★★ same type
ATP8A2 c.3272+1G>A Pathogenic/Likely pathogenic ★★ same type
ATP8A2 c.77-2A>G Pathogenic/Likely pathogenic ★★ same type
ATP8A2 p.Arg586Ter Pathogenic/Likely pathogenic ★★ same type
ATP8A2 p.Asp765Tyr Likely pathogenic ★★ same type
ATP8A2 p.Ala1091Val Uncertain significance ★★ ⚠ same type
ATP8A2 p.Ala335Thr 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/atp8a2-p-arg142ter (accessed [today's date]).

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