Is PAX5 p.Pro80Arg (c.239C>G) pathogenic?

PAX5 p.Pro80Arg (c.239C>G) is classified Likely pathogenic in PAX5 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-09-23). AlphaMissense: likely pathogenic (0.9988); Absent from gnomAD v4.1; Associated with acute lymphoblastic leukemia.

What condition is associated with PAX5 p.Pro80Arg (c.239C>G)?

PAX5 p.Pro80Arg (c.239C>G) is associated with acute lymphoblastic leukemia (ClinVar).

How common is PAX5 p.Pro80Arg (c.239C>G) in the general population?

PAX5 p.Pro80Arg (c.239C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PAX5 p.Pro80Arg (c.239C>G)?

AlphaMissense predicts likely pathogenic (score 0.9988) — an in-silico prediction, not a clinical call.

PAX5 p.Pro80Arg

c.239C>G · rs2494512979 · VCV624590

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9988 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

acute lymphoblastic leukemia

Computational evidence

Protein change
AlphaMissense	0.9988	likely pathogenic ✓ concordant with ClinVar
REVEL	0.969	strongly pathogenic-leaning
SaProt	LLR -16.55	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.9, phastCons 1
Regional constraint	o/e 0.47	unconstrained · MANE · 153 bp · p 7.7e-06 · regional, not allelic
Overall
CADD	31.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Cancer therapy — CIViC

Disease	Level	Significance
B-lymphoblastic Leukemia With PAX5 P.P80R	B	Positive
B-lymphoblastic Leukemia With PAX5 P.P80R	D	Oncogenicity
B-lymphoblastic Leukemia With PAX5 P.P80R	B	Positive
B-lymphoblastic Leukemia With PAX5 P.P80R	B	Positive

Variant & gene context

Gene: PAX5
Protein: p.Pro80Arg
Coding: c.239C>G
MANE Select: NM_016734
dbSNP: rs2494512979
Type: single nucleotide variant
Location: chr9:37015168 (GRCh38)
Gene constraint: LOEUF 0.361 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 63.89 · 2 PDB
Residue 80: a DNA-binding region; a UniProt-annotated variant site (sequence variant); an α-helix

Full PAX5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

acute lymphoblastic leukemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PAX5 p.Pro80= Likely benign ★ same residue
PAX5 c.46+1G>A Likely pathogenic ★ same condition
PAX5 p.Glu205Ter Likely pathogenic ★ same condition
PAX5 p.Gly323Ter Likely pathogenic ★ same condition
PAX5 p.Pro130Thr Likely pathogenic ★ same condition
PAX5 p.Ser134Cys Likely pathogenic ★ same condition
PAX5 p.Trp358Ter Likely pathogenic ★ same condition
PAX5 p.Val26Gly Likely pathogenic ★ same condition

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/pax5-p-pro80arg (accessed [today's date]).

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