Is AZGP1 p.Ala276Ser (c.826G>T) pathogenic?

AZGP1 p.Ala276Ser (c.826G>T) is classified Uncertain significance in AZGP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-21). AlphaMissense: likely benign (0.0739); Very rare (popmax 0.00492%, nfe).

How common is AZGP1 p.Ala276Ser (c.826G>T) in the general population?

AZGP1 p.Ala276Ser (c.826G>T) is very rare (popmax 0.00492%, nfe) (gnomAD).

What do computational predictors say about AZGP1 p.Ala276Ser (c.826G>T)?

AlphaMissense predicts likely benign (score 0.0739) — an in-silico prediction, not a clinical call.

AZGP1 p.Ala276Ser

c.826G>T · VCV3258375

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0739 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00492%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0739	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	LLR -5.61	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 0.34	GERP -0.78, phastCons 0.001
Regional constraint	o/e 0.97	unconstrained · MANE · 9,014 bp · p 0.57 · regional, not allelic
Overall
CADD	5.588	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 0.00492% European (non-Finnish) · 58/1,180,050 alleles

Filtering AF 0.00386% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00353%

Overall 0.00366% 59/1,614,084 alleles · very rare exomes 56/1,461,886 · genomes 3/152,198 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00492%	20,346
African / African-American	0.00133%	74,910

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.Ala276Ser
Coding: c.826G>T
MANE Select: NM_001185
Type: single nucleotide variant
Location: chr7:99967074 (GRCh38)
Gene constraint: LOEUF 1.141 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.26 · 10 PDB
Residue 276: the ig-like c1-type domain

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

Similar variants

AZGP1 p.Ala276Asp Uncertain significance ★ ⚠ same residue
AZGP1 p.Ala276Val Uncertain significance ★ ⚠ same residue
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.Arg120Trp Uncertain significance ★ ⚠ same type
AZGP1 p.Arg177Gln 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-ala276ser (accessed [today's date]).

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