Is AGXT p.Asn72= (c.216C>T) pathogenic?

AGXT p.Asn72= (c.216C>T) is classified Likely benign in AGXT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-22). Very rare (popmax 0.000254%, nfe).

How common is AGXT p.Asn72= (c.216C>T) in the general population?

AGXT p.Asn72= (c.216C>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

AGXT p.Asn72=

c.216C>T · rs202108064 · VCV1972288

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.36	GERP -2.5
Overall
CADD	4.704	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,180,022 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,461,652 alleles · very rare

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: AGXT
Protein: p.Asn72=
Coding: c.216C>T
MANE Select: NM_000030
dbSNP: rs202108064
Type: single nucleotide variant
Location: chr2:240869220 (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.Asn72Asp Conflicting classifications of pathogenicity ★ ⚠ same residue
AGXT p.Asn72His Conflicting classifications of pathogenicity ★ ⚠ same residue
AGXT p.Asn72Lys Conflicting classifications of pathogenicity ★ ⚠ 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-asn72 (accessed [today's date]).

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