Is AZGP1 p.Pro70Ala (c.208C>G) pathogenic?

AZGP1 p.Pro70Ala (c.208C>G) is classified Uncertain significance in AZGP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-05). AlphaMissense: likely benign (0.2077); Very rare (popmax 0.00167%, amr).

How common is AZGP1 p.Pro70Ala (c.208C>G) in the general population?

AZGP1 p.Pro70Ala (c.208C>G) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about AZGP1 p.Pro70Ala (c.208C>G)?

AlphaMissense predicts likely benign (score 0.2077) — an in-silico prediction, not a clinical call.

AZGP1 p.Pro70Ala

c.208C>G · VCV3814996

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2077 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2077	likely benign
REVEL	0.317	indeterminate
SaProt	LLR -11.05	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 9,014 bp · p 0.57 · regional, not allelic
Overall
CADD	20.6	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 0.00167% Admixed American · 1/59,998 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.00062% 10/1,614,056 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,998
European (non-Finnish)	0.000763%	131,115

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.Pro70Ala
Coding: c.208C>G
MANE Select: NM_001185
Type: single nucleotide variant
Location: chr7:99971875 (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-pro70ala (accessed [today's date]).

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