Is AGXT2 p.Arg502Leu (c.1505G>T) pathogenic?

AGXT2 p.Arg502Leu (c.1505G>T) is classified Uncertain significance in AGXT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: likely benign (0.1296); Absent from gnomAD v4.1.

How common is AGXT2 p.Arg502Leu (c.1505G>T) in the general population?

AGXT2 p.Arg502Leu (c.1505G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AGXT2 p.Arg502Leu (c.1505G>T)?

AlphaMissense predicts likely benign (score 0.1296) — an in-silico prediction, not a clinical call.

AGXT2 p.Arg502Leu

c.1505G>T · VCV4253760

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1296 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1296	likely benign
REVEL	0.098	moderately benign-leaning
SaProt	LLR -12.06	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.39	GERP -2.5
Regional constraint	o/e 1.04	unconstrained · MANE · 49 kb · p 0.33 · regional, not allelic
Overall
CADD	8.492	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

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: AGXT2
Protein: p.Arg502Leu
Coding: c.1505G>T
MANE Select: NM_031900
Type: single nucleotide variant
Location: chr5:34998759 (GRCh38)
Gene constraint: LOEUF 1.185 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.02

Full AGXT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AGXT2 p.Arg502Cys Uncertain significance ★ ⚠ same residue
AGXT2 c.1188+1G>A Benign/Likely benign ★★ same type
AGXT2 p.Arg133Cys Benign ★★ ⚠ same type
AGXT2 p.Arg242Gln Benign ★★ same type
AGXT2 p.Tyr203= Benign ★★ same type
AGXT2 p.Val116= Likely benign ★★ same type
AGXT2 p.Ala183Val Uncertain significance ★ ⚠ same type
AGXT2 p.Ala306Gly 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/agxt2-p-arg502leu (accessed [today's date]).

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