Is ATP2C1 p.Pro863Ser (c.2587C>T) pathogenic?

ATP2C1 p.Pro863Ser (c.2587C>T) is classified Uncertain significance in ATP2C1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-01). AlphaMissense: ambiguous (0.4207); Very rare (popmax 0.00133%, afr).

How common is ATP2C1 p.Pro863Ser (c.2587C>T) in the general population?

ATP2C1 p.Pro863Ser (c.2587C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about ATP2C1 p.Pro863Ser (c.2587C>T)?

AlphaMissense predicts ambiguous (score 0.4207) — an in-silico prediction, not a clinical call.

ATP2C1 p.Pro863Ser

c.2587C>T · rs762718343 · VCV3026968

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4207 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4207	ambiguous
REVEL	0.769	pathogenic-leaning
SaProt	LLR -10.64	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.9, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 3,735 bp · p 2e-05 · regional, not allelic
Overall
CADD	27.6	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,916 alleles

Overall 0.000124% 2/1,613,414 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,916
European (non-Finnish)	8.48e-05%	1,179,622

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: ATP2C1
Protein: p.Pro863Ser
Coding: c.2587C>T
MANE Select: NM_001378687
dbSNP: rs762718343
Type: single nucleotide variant
Location: chr3:130999617 (GRCh38)
Gene constraint: LOEUF 0.402 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.33 · 11 PDB
Residue 863: an α-helix; a UniProt-annotated variant site (in hhd)

Full ATP2C1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATP2C1 p.Pro863= Uncertain significance ★ same residue
ATP2C1 c.1308+1G>T Pathogenic ★★ same type
ATP2C1 c.2058-1G>A Pathogenic ★★ same type
ATP2C1 p.Arg153Ter Pathogenic ★★ same type
ATP2C1 p.Arg799Ter Pathogenic ★★ same type
ATP2C1 p.Arg806Ter Pathogenic ★★ same type
ATP2C1 p.Asn738Ser Likely pathogenic ★★ same type
ATP2C1 p.Ile580Val Likely pathogenic ★★ ⚠ 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/atp2c1-p-pro863ser (accessed [today's date]).

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