Is ATP2C2 p.Ile150Met (c.450C>G) pathogenic?

ATP2C2 p.Ile150Met (c.450C>G) is classified Benign in ATP2C2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-04-25). AlphaMissense: likely benign (0.125); Low-frequency (popmax 1.22%, eas); Associated with ATP2C2-related disorder.

What condition is associated with ATP2C2 p.Ile150Met (c.450C>G)?

ATP2C2 p.Ile150Met (c.450C>G) is associated with ATP2C2-related disorder (ClinVar).

How common is ATP2C2 p.Ile150Met (c.450C>G) in the general population?

ATP2C2 p.Ile150Met (c.450C>G) is low-frequency (popmax 1.22%, eas) (gnomAD).

What do computational predictors say about ATP2C2 p.Ile150Met (c.450C>G)?

AlphaMissense predicts likely benign (score 0.125) — an in-silico prediction, not a clinical call.

ATP2C2 p.Ile150Met

c.450C>G · rs80149007 · VCV3052394

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.125 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.22%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

ATP2C2-related disorder

Computational evidence

Protein change
AlphaMissense	0.125	likely benign
REVEL	0.551	indeterminate
SaProt	LLR -7.75	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 1.1	GERP -2.6, phastCons 1
Regional constraint	o/e 1.59	unconstrained · MANE · 95 kb · p 2.4e-95 · regional, not allelic
Overall
CADD	20.5	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 1.22% East Asian · 549/44,880 alleles

Filtering AF 1.14% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.11%

Overall 0.0369% 595/1,614,144 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.22%	82
Remaining individualsnot grpmax-eligible	0.0368%	2,718
South Asian	0.011%	9,107
Admixed American	0.00167%	60,018
European (non-Finnish)	0.00102%	98,333

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.Ile150Met
Coding: c.450C>G
MANE Select: NM_014861
dbSNP: rs80149007
Type: single nucleotide variant
Location: chr16:84410600 (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

Disease context

ATP2C2-related disorder

Similar variants

ATP2C2 p.Ile150Phe Uncertain significance ★ ⚠ same residue
ATP2C2 p.Ile150= Likely benign ★ same residue
ATP2C2 c.2580+1G>A Uncertain significance same condition
ATP2C2 p.Ala223Asp Uncertain significance ⚠ same condition
ATP2C2 c.1210-10C>T Likely benign same condition
ATP2C2 c.1504-3A>G Likely benign same condition
ATP2C2 c.1980+6C>T Likely benign same condition
ATP2C2 c.2217-5C>T Likely benign same condition

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-ile150met (accessed [today's date]).

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