Is AZGP1 p.Pro6Ser (c.16C>T) pathogenic?

AZGP1 p.Pro6Ser (c.16C>T) is classified Uncertain significance in AZGP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-27). AlphaMissense: likely benign (0.1223); Ultra-rare (popmax 0.0538%, sas).

How common is AZGP1 p.Pro6Ser (c.16C>T) in the general population?

AZGP1 p.Pro6Ser (c.16C>T) is ultra-rare (popmax 0.0538%, sas) (gnomAD).

What do computational predictors say about AZGP1 p.Pro6Ser (c.16C>T)?

AlphaMissense predicts likely benign (score 0.1223) — an in-silico prediction, not a clinical call.

AZGP1 p.Pro6Ser

c.16C>T · rs151090185 · VCV3132497

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1223 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0538%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1223	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -6.82	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP -1.5, phastCons 0.99
Regional constraint	o/e 0.97	unconstrained · MANE · 9,014 bp · p 0.57 · regional, not allelic
Overall
CADD	4.818	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0538% South Asian · 49/91,090 alleles

Filtering AF 0.0417% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0374%

Overall 0.0182% 294/1,613,942 alleles · ultra-rare exomes 272/1,461,850 · genomes 22/152,092 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0538%	1,859
European (non-Finnish)	0.0187%	5,339
Remaining individualsnot grpmax-eligible	0.016%	6,249
East Asian	0.0134%	7,479
Admixed American	0.005%	19,999
Finnishnot grpmax-eligible	0.00469%	21,339
African / African-American	0.00267%	37,444

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: AZGP1
Protein: p.Pro6Ser
Coding: c.16C>T
MANE Select: NM_001185
dbSNP: rs151090185
Type: single nucleotide variant
Location: chr7:99976005 (GRCh38)
Gene constraint: LOEUF 1.141 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.26 · 10 PDB

Full AZGP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AZGP1 p.Ala133Thr Uncertain significance ★ ⚠ same type
AZGP1 p.Ala161Asp Uncertain significance ★ ⚠ same type
AZGP1 p.Ala188Val Uncertain significance ★ ⚠ same type
AZGP1 p.Ala18Thr Uncertain significance ★ ⚠ same type
AZGP1 p.Ala276Asp Uncertain significance ★ ⚠ same type
AZGP1 p.Ala276Ser Uncertain significance ★ ⚠ same type
AZGP1 p.Ala276Val Uncertain significance ★ ⚠ same type
AZGP1 p.Arg120Trp 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/azgp1-p-pro6ser (accessed [today's date]).

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