Is AGXT p.Ala13Pro (c.37G>C) pathogenic?

AGXT p.Ala13Pro (c.37G>C) is classified Uncertain significance in AGXT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-06). AlphaMissense: likely benign (0.1257); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with AGXT p.Ala13Pro (c.37G>C)?

AGXT p.Ala13Pro (c.37G>C) is associated with Inborn genetic diseases (ClinVar).

How common is AGXT p.Ala13Pro (c.37G>C) in the general population?

AGXT p.Ala13Pro (c.37G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AGXT p.Ala13Pro (c.37G>C)?

AlphaMissense predicts likely benign (score 0.1257) — an in-silico prediction, not a clinical call.

AGXT p.Ala13Pro

c.37G>C · rs2528738973 · VCV2557073

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1257 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1257	likely benign
REVEL	0.345	indeterminate
SaProt	LLR -7.48	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	GERP -1.2, phastCons 0.6
Regional constraint	o/e 1.00	unconstrained · MANE · 9,952 bp · p 0.92 · regional, not allelic
Overall
CADD	16.65	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AGXT
Protein: p.Ala13Pro
Coding: c.37G>C
MANE Select: NM_000030
dbSNP: rs2528738973
Type: single nucleotide variant
Location: chr2:240868902 (GRCh38)
Gene constraint: LOEUF 1.251 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 98.30 · 17 PDB
Residue 13: an α-helix

Full AGXT 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

AGXT p.Ala13= Likely benign ★ same residue
AGXT p.Ser81Leu Pathogenic/Likely pathogenic ★★ same condition
AGXT c.847-3C>T Uncertain significance ★★ same condition
AGXT p.Ala296Val Uncertain significance ★★ ⚠ same condition
AGXT p.Ala382Val Uncertain significance ★★ ⚠ same condition
AGXT p.Val266Ile Uncertain significance ★★ ⚠ same condition
AGXT p.Ala13fs Likely pathogenic ★ same residue
AGXT p.Ala248Ser Conflicting classifications of pathogenicity ★ ⚠ 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/agxt-p-ala13pro (accessed [today's date]).

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