Is AZU1 p.Pro39Ser (c.115C>T) pathogenic?

AZU1 p.Pro39Ser (c.115C>T) is classified Uncertain significance in AZU1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-21). AlphaMissense: ambiguous (0.4959); Very rare (popmax 0.00446%, eas).

How common is AZU1 p.Pro39Ser (c.115C>T) in the general population?

AZU1 p.Pro39Ser (c.115C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about AZU1 p.Pro39Ser (c.115C>T)?

AlphaMissense predicts ambiguous (score 0.4959) — an in-silico prediction, not a clinical call.

AZU1 p.Pro39Ser

c.115C>T · VCV4189034

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4959 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Computational evidence

Protein change
AlphaMissense	0.4959	ambiguous
REVEL	0.602	indeterminate
SaProt	LLR -9.41	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP 0.62, phastCons 0.15
Regional constraint	o/e 1.04	unconstrained · MANE · 4,027 bp · p 0.4 · regional, not allelic
Overall
CADD	22.3	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 0.00446% East Asian · 2/44,862 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000274% 4/1,459,478 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,431
Remaining individualsnot grpmax-eligible	0.0016%	62,424
South Asian	0.0011%	90,954

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: AZU1
Protein: p.Pro39Ser
Coding: c.115C>T
MANE Select: NM_001700
Type: single nucleotide variant
Location: chr19:828286 (GRCh38)
Gene constraint: LOEUF 1.73 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.27 · 4 PDB
Residue 39: the peptidase s1 domain

Full AZU1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AZU1 p.Pro39Leu Uncertain significance ★ ⚠ same residue
AZU1 p.Ala145Asp Uncertain significance ★ ⚠ same type
AZU1 p.Ala33Ser Uncertain significance ★ ⚠ same type
AZU1 p.Ala55Thr Uncertain significance ★ ⚠ same type
AZU1 p.Ala55Val Uncertain significance ★ ⚠ same type
AZU1 p.Ala59Gly Uncertain significance ★ ⚠ same type
AZU1 p.Ala65Val Uncertain significance ★ ⚠ same type
AZU1 p.Arg158Cys 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/azu1-p-pro39ser (accessed [today's date]).

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