Is PAX5 p.Pro320Arg (c.959C>G) pathogenic?

PAX5 p.Pro320Arg (c.959C>G) is classified Uncertain significance in PAX5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-18). AlphaMissense: likely pathogenic (0.8207); Absent from gnomAD v4.1.

How common is PAX5 p.Pro320Arg (c.959C>G) in the general population?

PAX5 p.Pro320Arg (c.959C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PAX5 p.Pro320Arg (c.959C>G)?

AlphaMissense predicts likely pathogenic (score 0.8207) — an in-silico prediction, not a clinical call.

PAX5 p.Pro320Arg

c.959C>G · rs2131763339 · VCV2446680

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8207 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8207	likely pathogenic
REVEL	0.497	indeterminate
SaProt	LLR -8.80	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 166 kb · p 0.0054 · regional, not allelic
Overall
CADD	29.1	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.

Variant & gene context

Gene: PAX5
Protein: p.Pro320Arg
Coding: c.959C>G
MANE Select: NM_016734
dbSNP: rs2131763339
Type: single nucleotide variant
Location: chr9:36882057 (GRCh38)
Gene constraint: LOEUF 0.361 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 63.89 · 2 PDB

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

Similar variants

PAX5 p.Pro320Leu Uncertain significance ★ same residue
PAX5 p.Pro320Ser Uncertain significance ★ same residue
PAX5 p.Pro320Thr Uncertain significance ★ same residue
PAX5 p.Pro320= Likely benign ★ same residue
PAX5 c.1013-1G>A Uncertain significance ★★ same type
PAX5 p.Ala308Thr Uncertain significance ★★ ⚠ same type
PAX5 p.Ala376Thr Uncertain significance ★★ ⚠ same type
PAX5 p.Ala383Val 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/pax5-p-pro320arg (accessed [today's date]).

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