Is ATP2B4 p.Ser1053Phe (c.3158C>T) pathogenic?

ATP2B4 p.Ser1053Phe (c.3158C>T) is classified Benign in ATP2B4 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-27). Low-frequency (popmax 1.3%, nfe).

How common is ATP2B4 p.Ser1053Phe (c.3158C>T) in the general population?

ATP2B4 p.Ser1053Phe (c.3158C>T) is low-frequency (popmax 1.3%, nfe) (gnomAD).

ATP2B4 p.Ser1053Phe

c.3158C>T · rs148156799 · VCV703803

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.3%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.362	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP 0.86, phastCons 0.98
Regional constraint	o/e 0.49	unconstrained · MANE · 16 kb · p 1.9e-08 · regional, not allelic
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.3% European (non-Finnish) · 15,304/1,180,020 alleles

Filtering AF 1.28% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.27%

Overall 1.08% 17,496/1,614,186 alleles · low-frequency

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.63%	61
European (non-Finnish)grpmax	1.3%	77
Remaining individualsnot grpmax-eligible	0.803%	125
Finnishnot grpmax-eligible	0.748%	134
Admixed American	0.596%	168
Middle Eastern	0.363%	276
South Asian	0.238%	420
African / African-American	0.173%	577
East Asian	0.00223%	44,878

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: ATP2B4
Protein: p.Ser1053Phe
Coding: c.3158C>T
MANE Select: NM_001684
dbSNP: rs148156799
Type: single nucleotide variant
Location: chr1:203727420 (GRCh38)
Gene constraint: LOEUF 0.44 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.71 · 2 PDB

Full ATP2B4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATP2B4 p.Arg554Cys Uncertain significance ★★ same type
ATP2B4 p.Arg624Cys Uncertain significance ★★ same type
ATP2B4 p.Arg732Cys Uncertain significance ★★ same type
ATP2B4 p.Arg993Gly Uncertain significance ★★ same type
ATP2B4 p.Asn851Ser Uncertain significance ★★ same type
ATP2B4 p.Asp333Gly Uncertain significance ★★ same type
ATP2B4 p.Asp502Asn Uncertain significance ★★ same type
ATP2B4 p.Gly634Arg 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/atp2b4-p-ser1053phe (accessed [today's date]).

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