Is CIP2A p.Ser53Gly (c.157A>G) pathogenic?

CIP2A p.Ser53Gly (c.157A>G) is classified Uncertain significance in CIP2A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: likely benign (0.0915); Very rare (popmax 0.00333%, amr).

How common is CIP2A p.Ser53Gly (c.157A>G) in the general population?

CIP2A p.Ser53Gly (c.157A>G) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about CIP2A p.Ser53Gly (c.157A>G)?

AlphaMissense predicts likely benign (score 0.0915) — an in-silico prediction, not a clinical call.

CIP2A p.Ser53Gly

c.157A>G · VCV4229116

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0915 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0915	likely benign
REVEL	0.199	benign-leaning
SaProt	LLR -7.92	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.26	donor gain · deltas
Pangolin	Δ0.20	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 5	GERP -0.046, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 38 kb · p 0.12 · regional, not allelic
Overall
CADD	23.5	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 0.00333% Admixed American · 2/60,018 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000137% 2/1,461,108 alleles · very rare

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.Ser53Gly
Coding: c.157A>G
MANE Select: NM_020890
Type: single nucleotide variant
Location: chr3:108585158 (GRCh38)
Gene constraint: LOEUF 1.057 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.09 · 1 PDB
Residue 53: an α-helix

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-ser53gly (accessed [today's date]).

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