Is PAX5 p.Pro320Ser (c.958C>T) pathogenic?

PAX5 p.Pro320Ser (c.958C>T) is classified Uncertain significance in PAX5 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-03-15). AlphaMissense: ambiguous (0.364); Very rare (popmax 8.49e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PAX5 p.Pro320Ser (c.958C>T)?

PAX5 p.Pro320Ser (c.958C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PAX5 p.Pro320Ser (c.958C>T) in the general population?

PAX5 p.Pro320Ser (c.958C>T) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

What do computational predictors say about PAX5 p.Pro320Ser (c.958C>T)?

AlphaMissense predicts ambiguous (score 0.364) — an in-silico prediction, not a clinical call.

PAX5 p.Pro320Ser

c.958C>T · VCV4861587

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.364 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.364	ambiguous
REVEL	0.387	indeterminate
SaProt	LLR -6.16	tolerated
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.9	GERP 2.5, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 166 kb · p 0.0054 · regional, not allelic
Overall
CADD	27.2	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 8.49e-05% European (non-Finnish) · 1/1,178,404 alleles

Overall 6.21e-05% 1/1,611,592 alleles · very rare exomes 1/1,459,310 · genomes 0/152,282 · joint denominator

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: PAX5
Protein: p.Pro320Ser
Coding: c.958C>T
MANE Select: NM_016734
Type: single nucleotide variant
Location: chr9:36882058 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PAX5 p.Pro320Leu Uncertain significance ★ same residue
PAX5 p.Pro320Thr Uncertain significance ★ same residue
PAX5 p.Pro320= Likely benign ★ same residue
PAX5 p.Pro320Arg Uncertain significance ★ ⚠ same residue
PAX5 p.Ala308Thr Uncertain significance ★★ ⚠ same condition
PAX5 p.Ala383Val Uncertain significance ★★ ⚠ same condition
PAX5 p.Ala45Ser Uncertain significance ★★ ⚠ same condition
PAX5 p.Arg122Gln Uncertain significance ★★ ⚠ 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-pro320ser (accessed [today's date]).

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