Is ATP2C2 p.Arg897Ser (c.2691G>C) pathogenic?

ATP2C2 p.Arg897Ser (c.2691G>C) is classified Benign in ATP2C2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.1503); Common (popmax 5.12%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about ATP2C2 p.Arg897Ser (c.2691G>C)?

AlphaMissense predicts likely benign (score 0.1503) — an in-silico prediction, not a clinical call.

ATP2C2 p.Arg897Ser

Q: How common is ATP2C2 p.Arg897Ser (c.2691G>C) in the general population?

ATP2C2 p.Arg897Ser (c.2691G>C) is common (popmax 5.12%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2691G>C · rs62640935 · VCV788457

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1503 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 5.12%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1503	likely benign
REVEL	0.308	indeterminate
SaProt	LLR -5.69	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 3.2	GERP -0.98, phastCons 1
Regional constraint	o/e 1.59	unconstrained · MANE · 95 kb · p 2.4e-95 · regional, not allelic
Overall
CADD	18.48	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 5.12% African / African-American · 3,843/75,030 alleles

Filtering AF 4.99% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.93%

Overall 0.27% 4,352/1,613,928 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.12%	20
Remaining individualsnot grpmax-eligible	0.336%	298
Admixed American	0.322%	311
Middle Eastern	0.264%	379
South Asian	0.0264%	3,794
European (non-Finnish)	0.00559%	17,877

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: ATP2C2
Protein: p.Arg897Ser
Coding: c.2691G>C
MANE Select: NM_014861
dbSNP: rs62640935
Type: single nucleotide variant
Location: chr16:84462098 (GRCh38)
Gene constraint: LOEUF 1.712 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 81.13

Full ATP2C2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATP2C2 p.Arg897Gly Uncertain significance ★ ⚠ same residue
ATP2C2 p.Ala813Val Uncertain significance ★★ ⚠ same type
ATP2C2 p.Tyr877Ser Uncertain significance ★★ ⚠ same type
ATP2C2 c.2148-9C>G Benign ★★ same type
ATP2C2 c.2334-8C>T Benign ★★ same type
ATP2C2 c.2481+7G>T Benign ★★ same type
ATP2C2 c.2482-19C>G Benign ★★ same type
ATP2C2 c.2482-2A>C Benign ★★ 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/atp2c2-p-arg897ser (accessed [today's date]).

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