Is AGXT p.Cys173= (c.519C>T) pathogenic?

AGXT p.Cys173= (c.519C>T) is classified Likely benign in AGXT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-22). Very rare (popmax 0.003%, nfe).

How common is AGXT p.Cys173= (c.519C>T) in the general population?

AGXT p.Cys173= (c.519C>T) is very rare (popmax 0.003%, nfe) (gnomAD).

AGXT p.Cys173=

c.519C>T · rs180177232 · VCV1079324

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.003%, 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 0.13	GERP -1.6, phastCons 0.96
Overall
CADD	7.876	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.003% European (non-Finnish) · 35/1,166,866 alleles

Filtering AF 0.00218% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00193%

Overall 0.00227% 36/1,586,318 alleles · very rare exomes 35/1,434,116 · genomes 1/152,202 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.003%	33,339
Remaining individualsnot grpmax-eligible	0.00163%	61,444

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.Cys173=
Coding: c.519C>T
MANE Select: NM_000030
dbSNP: rs180177232
Type: single nucleotide variant
Location: chr2:240871444 (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 173: a UniProt-annotated variant site (in hp1; loss of alanine--glyoxylate aminotransferase activity; loss of dimerization; decreased protein stability; causes protein aggregation); an α-helix

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

Similar variants

AGXT p.Cys173Ter Pathogenic ★ same residue
AGXT p.Cys173Tyr Likely pathogenic ★ same residue
AGXT p.Cys173Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
AGXT p.Cys173_His174delinsTrpAsn Pathogenic/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
AGXT c.524+2T>A 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-cys173 (accessed [today's date]).

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