Is AGXT p.Asn72Asp (c.214A>G) pathogenic?

AGXT p.Asn72Asp (c.214A>G) is classified Conflicting classifications of pathogenicity in AGXT (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-07-09). AlphaMissense: likely pathogenic (0.6322); Absent from gnomAD v4.1.

How common is AGXT p.Asn72Asp (c.214A>G) in the general population?

AGXT p.Asn72Asp (c.214A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AGXT p.Asn72Asp (c.214A>G)?

AlphaMissense predicts likely pathogenic (score 0.6322) — an in-silico prediction, not a clinical call.

AGXT p.Asn72Asp

c.214A>G · rs754637713 · VCV1490938

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6322 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6322	likely pathogenic
REVEL	0.841	moderately pathogenic-leaning
SaProt	LLR -11.60	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.30 · evaluated, not missing
Constraint at this position
Conservation	phyloP 11	GERP 1.3, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 9,952 bp · p 0.92 · regional, not allelic
Overall
CADD	25.9	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: AGXT
Protein: p.Asn72Asp
Coding: c.214A>G
MANE Select: NM_000030
dbSNP: rs754637713
Type: single nucleotide variant
Location: chr2:240869218 (GRCh38)
Gene constraint: LOEUF 1.251 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 98.30 · 17 PDB

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

Similar variants

AGXT p.Asn72Ile Pathogenic/Likely pathogenic ★★ same residue
AGXT p.Asn72His Conflicting classifications of pathogenicity ★ ⚠ same residue
AGXT p.Asn72Lys Conflicting classifications of pathogenicity ★ ⚠ same residue
AGXT p.Asn72= Likely benign ★ same residue
AGXT p.Asn72fs Likely pathogenic ★ same residue
AGXT c.358+1G>A Pathogenic ★★ same type
AGXT c.359-2A>G Likely pathogenic ★★ same type
AGXT c.423+1G>A Pathogenic/Likely pathogenic ★★ 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/agxt-p-asn72asp (accessed [today's date]).

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