Is ATP2A3 p.Ala4Ser (c.10G>T) pathogenic?

ATP2A3 p.Ala4Ser (c.10G>T) is classified Uncertain significance in ATP2A3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-09). AlphaMissense: likely benign (0.1387); Absent from gnomAD v4.1.

How common is ATP2A3 p.Ala4Ser (c.10G>T) in the general population?

ATP2A3 p.Ala4Ser (c.10G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ATP2A3 p.Ala4Ser (c.10G>T)?

AlphaMissense predicts likely benign (score 0.1387) — an in-silico prediction, not a clinical call.

ATP2A3 p.Ala4Ser

c.10G>T · VCV4644252

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1387 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,270,052)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1387	likely benign
REVEL	0.456	indeterminate
SaProt	LLR -9.09	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP 1.3, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 14 kb · p 0.22 · regional, not allelic
Overall
CADD	21.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,270,052). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ATP2A3
Protein: p.Ala4Ser
Coding: c.10G>T
MANE Select: NM_005173
Type: single nucleotide variant
Location: chr17:3964282 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.75

Full ATP2A3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATP2A3 c.2525-6C>G Likely benign ★★ same type
ATP2A3 p.Ala299= Likely benign ★★ same type
ATP2A3 p.Arg491= Benign ★★ same type
ATP2A3 p.Arg560= Benign/Likely benign ★★ same type
ATP2A3 p.Arg674Cys Likely benign ★★ ⚠ same type
ATP2A3 p.Ile716= Benign/Likely benign ★★ same type
ATP2A3 p.Ser877= Benign ★★ same type
ATP2A3 c.2611-1G>C 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/atp2a3-p-ala4ser (accessed [today's date]).

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