Is ATP8A2 p.Ser723= (c.2169G>A) pathogenic?

ATP8A2 p.Ser723= (c.2169G>A) is classified Benign/Likely benign in ATP8A2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-03-01). Rare (popmax 0.183%, afr); Associated with cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 4.

What condition is associated with ATP8A2 p.Ser723= (c.2169G>A)?

ATP8A2 p.Ser723= (c.2169G>A) is associated with cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 4 (ClinVar).

How common is ATP8A2 p.Ser723= (c.2169G>A) in the general population?

ATP8A2 p.Ser723= (c.2169G>A) is rare (popmax 0.183%, afr) (gnomAD).

How is Dysequilibrium syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ATP8A2 p.Ser723=

c.2169G>A · rs41300574 · VCV994318

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.183%, afr)

Conditions

cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 4

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 -0.039	GERP -3.9, phastCons 0.014
Overall
CADD	7.927	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.183% African / African-American · 137/74,950 alleles

Filtering AF 0.158% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.148%

Overall 0.0745% 1,201/1,611,698 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.183%	547
Remaining individualsnot grpmax-eligible	0.0881%	1,135
European (non-Finnish)	0.0848%	1,179
Middle Eastern	0.0165%	6,058
East Asian	0.00893%	11,202
Admixed American	0.00501%	19,963
Finnishnot grpmax-eligible	0.00156%	64,004
South Asian	0.0011%	90,820

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.Ser723=
Coding: c.2169G>A
MANE Select: NM_016529
dbSNP: rs41300574
Type: single nucleotide variant
Location: chr13:25589657 (GRCh38)
Gene constraint: LOEUF 0.728 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 81.12
Residue 723: a UniProt-annotated variant site (in camrq4; uncertain significance)

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

Disease context

cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Dysequilibrium syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Neonatal
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

ATP8A2 c.1782+2T>C Pathogenic ★★ same condition
ATP8A2 c.2212-1G>C Pathogenic ★★ same condition
ATP8A2 c.3272+1G>A Pathogenic/Likely pathogenic ★★ same condition
ATP8A2 c.77-2A>G Pathogenic/Likely pathogenic ★★ same condition
ATP8A2 p.Arg586Ter Pathogenic/Likely pathogenic ★★ same condition
ATP8A2 p.Asp765Tyr Likely pathogenic ★★ same condition
ATP8A2 p.Arg1147Trp Uncertain significance ★★ ⚠ same condition
ATP8A2 p.Arg659Gln Uncertain significance ★★ ⚠ 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/atp8a2-p-ser723 (accessed [today's date]).

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