Is CIP2A p.Ser213Phe (c.638C>T) pathogenic?

CIP2A p.Ser213Phe (c.638C>T) is classified Benign in CIP2A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-06-18). AlphaMissense: ambiguous (0.4538); Low-frequency (popmax 4.98%, afr).

How common is CIP2A p.Ser213Phe (c.638C>T) in the general population?

CIP2A p.Ser213Phe (c.638C>T) is low-frequency (popmax 4.98%, afr) (gnomAD).

What do computational predictors say about CIP2A p.Ser213Phe (c.638C>T)?

AlphaMissense predicts ambiguous (score 0.4538) — an in-silico prediction, not a clinical call.

CIP2A p.Ser213Phe

c.638C>T · rs77545973 · VCV775891

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4538 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4.98%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4538	ambiguous
REVEL	0.172	moderately benign-leaning
SaProt	LLR -6.32	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 1.6, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 38 kb · p 0.12 · regional, not allelic
Overall
CADD	23.3	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 4.98% African / African-American · 3,705/74,340 alleles

Filtering AF 4.85% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.8%

Overall 0.267% 4,265/1,597,180 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.98%	20
Remaining individualsnot grpmax-eligible	0.365%	274
Admixed American	0.359%	279
Middle Eastern	0.232%	430
South Asian	0.0215%	4,646
European (non-Finnish)	0.0077%	12,988

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.Ser213Phe
Coding: c.638C>T
MANE Select: NM_020890
dbSNP: rs77545973
Type: single nucleotide variant
Location: chr3:108579600 (GRCh38)
Gene constraint: LOEUF 1.057 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.09 · 1 PDB
Residue 213: the 'required for interaction with ppp2r5c' region; 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.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
CIP2A p.Ala84Glu 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-ser213phe (accessed [today's date]).

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