Is ATP8A2 p.Asp821= (c.2463C>T) pathogenic?

ATP8A2 p.Asp821= (c.2463C>T) is classified Likely benign in ATP8A2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-20). Very rare (popmax 0.00644%, nfe).

How common is ATP8A2 p.Asp821= (c.2463C>T) in the general population?

ATP8A2 p.Asp821= (c.2463C>T) is very rare (popmax 0.00644%, nfe) (gnomAD).

ATP8A2 p.Asp821=

c.2463C>T · rs759374071 · VCV1629899

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00644%, nfe)

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 -20	GERP -4.8
Overall
CADD	0.084	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00644% European (non-Finnish) · 76/1,179,976 alleles

Filtering AF 0.00528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00482%

Overall 0.00551% 89/1,614,072 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0125%	8,002
European (non-Finnish)grpmax	0.00644%	15,526
Remaining individualsnot grpmax-eligible	0.0032%	31,255
South Asian	0.0022%	45,536
Admixed American	0.00167%	60,026

Finnish 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.Asp821=
Coding: c.2463C>T
MANE Select: NM_016529
dbSNP: rs759374071
Type: single nucleotide variant
Location: chr13:25769124 (GRCh38)
Gene constraint: LOEUF 0.728 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 81.12
Residue 821: a binding site; 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.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-asp821 (accessed [today's date]).

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