Is PIM2 p.Pro289Ser (c.865C>T) pathogenic?

PIM2 p.Pro289Ser (c.865C>T) is classified Uncertain significance in PIM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-30). AlphaMissense: likely benign (0.0829); Rare (popmax 0.134%, eas).

How common is PIM2 p.Pro289Ser (c.865C>T) in the general population?

PIM2 p.Pro289Ser (c.865C>T) is rare (popmax 0.134%, eas) (gnomAD).

What do computational predictors say about PIM2 p.Pro289Ser (c.865C>T)?

AlphaMissense predicts likely benign (score 0.0829) — an in-silico prediction, not a clinical call.

PIM2 p.Pro289Ser

c.865C>T · VCV3932533

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0829 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.134%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0829	likely benign
REVEL	0.028	moderately benign-leaning
SaProt	LLR -10.98	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 0.48, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 294 bp · p 0.13 · regional, not allelic
Overall
CADD	10.03	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 0.134% East Asian · 44/32,904 alleles

Filtering AF 0.102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0913%

Overall 0.00404% 48/1,187,270 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.134%	748
Remaining individualsnot grpmax-eligible	0.00428%	23,358
South Asian	0.0037%	27,046

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: PIM2
Protein: p.Pro289Ser
Coding: c.865C>T
MANE Select: NM_006875
Type: single nucleotide variant
Location: chrX:48914202 (GRCh38)
Structure: AlphaFold pLDDT 90.38 · 2 PDB

Full PIM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PIM2 p.Ala122Thr Uncertain significance ★ ⚠ same type
PIM2 p.Arg101Cys Uncertain significance ★ ⚠ same type
PIM2 p.Arg141Cys Uncertain significance ★ ⚠ same type
PIM2 p.Arg264Cys Uncertain significance ★ ⚠ same type
PIM2 p.Arg274Gln Uncertain significance ★ ⚠ same type
PIM2 p.Asp191Asn Uncertain significance ★ ⚠ same type
PIM2 p.Asp196Tyr Uncertain significance ★ ⚠ same type
PIM2 p.Gly138Ala 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/pim2-p-pro289ser (accessed [today's date]).

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