Is ATP2C2 p.Ile150Phe (c.448A>T) pathogenic?

ATP2C2 p.Ile150Phe (c.448A>T) is classified Uncertain significance in ATP2C2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-24). AlphaMissense: likely benign (0.0909); Very rare (popmax 0.000424%, nfe).

How common is ATP2C2 p.Ile150Phe (c.448A>T) in the general population?

ATP2C2 p.Ile150Phe (c.448A>T) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about ATP2C2 p.Ile150Phe (c.448A>T)?

AlphaMissense predicts likely benign (score 0.0909) — an in-silico prediction, not a clinical call.

ATP2C2 p.Ile150Phe

c.448A>T · rs1479094043 · VCV2529727

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0909 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0909	likely benign
REVEL	0.501	indeterminate
SaProt	LLR -6.20	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 3.4	GERP -5, phastCons 1
Regional constraint	o/e 1.59	unconstrained · MANE · 95 kb · p 2.4e-95 · regional, not allelic
Overall
CADD	18.6	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

Grpmax group 0.000424% European (non-Finnish) · 5/1,180,006 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,614,072 alleles · very rare exomes 5/1,461,840 · genomes 0/152,232 · joint denominator

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.Ile150Phe
Coding: c.448A>T
MANE Select: NM_014861
dbSNP: rs1479094043
Type: single nucleotide variant
Location: chr16:84410598 (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.Ile150= Likely benign ★ same residue
ATP2C2 p.Ile150Met Benign 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

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-ile150phe (accessed [today's date]).

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