Is PAX5 p.Pro207= (c.621G>A) pathogenic?

PAX5 p.Pro207= (c.621G>A) is classified Likely benign in PAX5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-14). Very rare (popmax 0.00833%, amr); Associated with Inborn genetic diseases.

What condition is associated with PAX5 p.Pro207= (c.621G>A)?

PAX5 p.Pro207= (c.621G>A) is associated with Inborn genetic diseases (ClinVar).

How common is PAX5 p.Pro207= (c.621G>A) in the general population?

PAX5 p.Pro207= (c.621G>A) is very rare (popmax 0.00833%, amr) (gnomAD).

PAX5 p.Pro207=

c.621G>A · VCV3719335

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

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 -8.3	GERP -5.4
Overall
CADD	1.542	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00833% Admixed American · 5/60,024 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00206%

Overall 0.000616% 9/1,461,764 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	12,005
European (non-Finnish)	0.000339%	294,993

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.Pro207=
Coding: c.621G>A
MANE Select: NM_016734
Type: single nucleotide variant
Location: chr9:36966708 (GRCh38)
Gene constraint: LOEUF 0.361 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 63.89 · 2 PDB
Residue 207: the 'disordered' region

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.Pro207Ala Uncertain significance ★ ⚠ same residue
PAX5 p.Pro207Ser Uncertain significance ★ ⚠ same residue
PAX5 p.Pro207Leu 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

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-pro207 (accessed [today's date]).

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