Is CIP2A p.Ile759Val (c.2275A>G) pathogenic?

CIP2A p.Ile759Val (c.2275A>G) is classified Benign in CIP2A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-01). AlphaMissense: likely benign (0.0941); Low-frequency (popmax 2.85%, mid).

How common is CIP2A p.Ile759Val (c.2275A>G) in the general population?

CIP2A p.Ile759Val (c.2275A>G) is low-frequency (popmax 2.85%, mid) (gnomAD).

What do computational predictors say about CIP2A p.Ile759Val (c.2275A>G)?

AlphaMissense predicts likely benign (score 0.0941) — an in-silico prediction, not a clinical call.

CIP2A p.Ile759Val

c.2275A>G · rs13071874 · VCV2654025

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0941 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.85%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0941	likely benign
REVEL	0.108	moderately benign-leaning
SaProt	LLR -6.47	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP -0.41, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 38 kb · p 0.12 · regional, not allelic
Overall
CADD	15.44	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 2.85% Middle Eastern · 163/5,724 alleles

Filtering AF 2.49% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.35%

Overall 0.921% 14,436/1,567,210 alleles · low-frequency

Ancestry group	Frequency	1 in
Middle Easterngrpmax	2.85%	35
Ashkenazi Jewishnot grpmax-eligible	2.16%	46
Finnishnot grpmax-eligible	1.16%	86
South Asian	1.14%	88
Remaining individualsnot grpmax-eligible	0.987%	101
European (non-Finnish)	0.936%	107
Admixed American	0.876%	114
Amishnot grpmax-eligible	0.219%	456
African / African-American	0.142%	706
East Asian	0.00226%	44,288

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: CIP2A
Protein: p.Ile759Val
Coding: c.2275A>G
MANE Select: NM_020890
dbSNP: rs13071874
Type: single nucleotide variant
Location: chr3:108554425 (GRCh38)
Gene constraint: LOEUF 1.057 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.09 · 1 PDB
Residue 759: a UniProt-annotated variant site (in)

Full CIP2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CIP2A p.Asp353= Likely benign ★★ same type
CIP2A p.His314Arg Benign ★★ same type
CIP2A p.Ser213Phe Benign ★★ same type
CIP2A p.Ala268Val Uncertain significance ★ ⚠ same type
CIP2A p.Ala26Gly Uncertain significance ★ ⚠ same type
CIP2A p.Ala362Thr Uncertain significance ★ ⚠ same type
CIP2A p.Ala535Thr Uncertain significance ★ ⚠ same type
CIP2A p.Ala695Val 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/cip2a-p-ile759val (accessed [today's date]).

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