Is CIP2A p.Ser9Phe (c.26C>T) pathogenic?

CIP2A p.Ser9Phe (c.26C>T) is classified Uncertain significance in CIP2A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-13). AlphaMissense: ambiguous (0.5039); Very rare (popmax 0.00666%, afr).

How common is CIP2A p.Ser9Phe (c.26C>T) in the general population?

CIP2A p.Ser9Phe (c.26C>T) is very rare (popmax 0.00666%, afr) (gnomAD).

What do computational predictors say about CIP2A p.Ser9Phe (c.26C>T)?

AlphaMissense predicts ambiguous (score 0.5039) — an in-silico prediction, not a clinical call.

CIP2A p.Ser9Phe

c.26C>T · rs550644081 · VCV3145093

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5039 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00666%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5039	ambiguous
REVEL	0.216	benign-leaning
SaProt	LLR -10.96	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 38 kb · p 0.12 · regional, not allelic
Overall
CADD	26.8	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 0.00666% African / African-American · 5/75,066 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.000929% 15/1,613,840 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0144%	6,944
African / African-Americangrpmax	0.00666%	15,013
European (non-Finnish)	8.48e-05%	1,179,851

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser9Phe
Coding: c.26C>T
MANE Select: NM_020890
dbSNP: rs550644081
Type: single nucleotide variant
Location: chr3:108589350 (GRCh38)
Gene constraint: LOEUF 1.057 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.09 · 1 PDB
Residue 9: 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-ser9phe (accessed [today's date]).

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