Is PIM3 p.Pro313Ser (c.937C>T) pathogenic?

PIM3 p.Pro313Ser (c.937C>T) is classified Benign in PIM3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-06-08). AlphaMissense: likely benign (0.0726); Low-frequency (popmax 3.54%, amr).

How common is PIM3 p.Pro313Ser (c.937C>T) in the general population?

PIM3 p.Pro313Ser (c.937C>T) is low-frequency (popmax 3.54%, amr) (gnomAD).

What do computational predictors say about PIM3 p.Pro313Ser (c.937C>T)?

AlphaMissense predicts likely benign (score 0.0726) — an in-silico prediction, not a clinical call.

PIM3 p.Pro313Ser

c.937C>T · rs138365598 · VCV771545

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0726 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.54%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0726	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -5.43	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 -5.7	GERP -3.4
Regional constraint	o/e 1.01	unconstrained · MANE · 2,176 bp · p 0.82 · regional, not allelic
Overall
CADD	0.073	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 3.54% Admixed American · 2,118/59,764 alleles

Filtering AF 3.42% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.37%

Overall 0.137% 2,202/1,611,116 alleles · low-frequency exomes 1,939/1,458,776 · genomes 263/152,340 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	3.54%	28
Remaining individualsnot grpmax-eligible	0.0802%	1,248
African / African-American	0.0227%	4,413
European (non-Finnish)	0.00136%	73,709
South Asian	0.0011%	90,842

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: PIM3
Protein: p.Pro313Ser
Coding: c.937C>T
MANE Select: NM_001001852
dbSNP: rs138365598
Type: single nucleotide variant
Location: chr22:49963083 (GRCh38)
Gene constraint: LOEUF 1.002 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.64

Full PIM3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PIM3 p.Asp32Glu Benign ★★ same type
PIM3 p.His222= Benign ★★ same type
PIM3 p.Val300Ala Benign ★★ same type
PIM3 p.Ala103Val Uncertain significance ★ ⚠ same type
PIM3 p.Ala31Gly Uncertain significance ★ ⚠ same type
PIM3 p.Ala31Val Uncertain significance ★ ⚠ same type
PIM3 p.Arg104Cys Uncertain significance ★ ⚠ same type
PIM3 p.Arg108His 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/pim3-p-pro313ser (accessed [today's date]).

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