Is ATP4A p.Ile145= (c.435C>T) pathogenic?

ATP4A p.Ile145= (c.435C>T) is classified Benign in ATP4A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-27). Common (popmax 14.6%, afr) — too common for a highly-penetrant pathogenic allele.

ATP4A p.Ile145=

Q: How common is ATP4A p.Ile145= (c.435C>T) in the general population?

ATP4A p.Ile145= (c.435C>T) is common (popmax 14.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.435C>T · rs60726757 · VCV1601769

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 14.6%, afr) — too common for a highly-penetrant pathogenic allele

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 -1.7	GERP -3.5
Overall
CADD	5.083	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 14.6% African / African-American · 10,910/74,894 alleles

Filtering AF 14.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 14.2%

Overall 1.07% 17,213/1,613,846 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	14.6%	7
East Asian	2.01%	50
Middle Eastern	1.85%	54
Remaining individualsnot grpmax-eligible	1.66%	60
Admixed American	1.49%	67
South Asian	1.31%	76
Ashkenazi Jewishnot grpmax-eligible	0.432%	231
European (non-Finnish)	0.172%	581
Finnishnot grpmax-eligible	0.00781%	12,804

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: ATP4A
Protein: p.Ile145=
Coding: c.435C>T
MANE Select: NM_000704
dbSNP: rs60726757
Type: single nucleotide variant
Location: chr19:35560918 (GRCh38)
Gene constraint: LOEUF 0.808 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.70

Full ATP4A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATP4A p.Ala104Thr Uncertain significance ★★ ⚠ same type
ATP4A p.Ala104Val Uncertain significance ★★ ⚠ same type
ATP4A p.Ala119Thr Uncertain significance ★★ ⚠ same type
ATP4A p.Ala170Ser Uncertain significance ★★ ⚠ same type
ATP4A p.Ala90Thr Uncertain significance ★★ ⚠ same type
ATP4A p.Arg607Trp Uncertain significance ★★ ⚠ same type
ATP4A p.Arg660His Uncertain significance ★★ ⚠ same type
ATP4A p.Arg668Cys 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/atp4a-p-ile145 (accessed [today's date]).

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