Is PAX5 p.Pro34= (c.102G>A) pathogenic?

PAX5 p.Pro34= (c.102G>A) is classified Likely benign in PAX5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-13). Very rare (popmax 0.00329%, sas); Associated with Inborn genetic diseases.

What condition is associated with PAX5 p.Pro34= (c.102G>A)?

PAX5 p.Pro34= (c.102G>A) is associated with Inborn genetic diseases (ClinVar).

How common is PAX5 p.Pro34= (c.102G>A) in the general population?

PAX5 p.Pro34= (c.102G>A) is very rare (popmax 0.00329%, sas) (gnomAD).

PAX5 p.Pro34=

c.102G>A · VCV3414557

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.15	GERP -0.94, phastCons 0.95
Overall
CADD	15.01	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,084 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.00062% 10/1,614,008 alleles · very rare exomes 9/1,461,876 · genomes 1/152,132 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,361
African / African-American	0.00267%	37,444
East Asian	0.00223%	44,900
Remaining individualsnot grpmax-eligible	0.0016%	62,482
European (non-Finnish)	0.000254%	393,345

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.Pro34=
Coding: c.102G>A
MANE Select: NM_016734
Type: single nucleotide variant
Location: chr9:37020746 (GRCh38)
Gene constraint: LOEUF 0.361 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 63.89 · 2 PDB
Residue 34: a DNA-binding region; a UniProt-annotated variant site (in); the 'pai subdomain' region; an α-helix

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.Pro34Leu 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
PAX5 p.Arg239Cys Uncertain significance ★★ ⚠ same condition
PAX5 p.Gln233Lys Uncertain significance ★★ ⚠ same condition
PAX5 p.Gly202Asp 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-pro34 (accessed [today's date]).

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