Is AGXT2 p.Asp189His (c.565G>C) pathogenic?

AGXT2 p.Asp189His (c.565G>C) is classified Uncertain significance in AGXT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-01). AlphaMissense: likely benign (0.3208); Absent from gnomAD v4.1.

How common is AGXT2 p.Asp189His (c.565G>C) in the general population?

AGXT2 p.Asp189His (c.565G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AGXT2 p.Asp189His (c.565G>C)?

AlphaMissense predicts likely benign (score 0.3208) — an in-silico prediction, not a clinical call.

AGXT2 p.Asp189His

c.565G>C · VCV4253771

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3208 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3208	likely benign
REVEL	0.669	pathogenic-leaning
SaProt	LLR -11.46	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.8, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 49 kb · p 0.33 · regional, not allelic
Overall
CADD	26.3	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.Asp189His
Coding: c.565G>C
MANE Select: NM_031900
Type: single nucleotide variant
Location: chr5:35035238 (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.Asp189Asn 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-asp189his (accessed [today's date]).

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