Is AGXT p.Phe152Cys (c.455T>G) pathogenic?

AGXT p.Phe152Cys (c.455T>G) is classified Likely pathogenic in AGXT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-08). AlphaMissense: likely pathogenic (0.63); Very rare (popmax 0.00268%, afr).

How common is AGXT p.Phe152Cys (c.455T>G) in the general population?

AGXT p.Phe152Cys (c.455T>G) is very rare (popmax 0.00268%, afr) (gnomAD).

What do computational predictors say about AGXT p.Phe152Cys (c.455T>G)?

AlphaMissense predicts likely pathogenic (score 0.63) — an in-silico prediction, not a clinical call.

AGXT p.Phe152Cys

c.455T>G · rs765812098 · VCV1517157

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.63 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00268%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.63	likely pathogenic ✓ concordant with ClinVar
REVEL	0.83	moderately pathogenic-leaning
SaProt	LLR -9.48	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 9,952 bp · p 0.92 · regional, not allelic
Overall
CADD	26.7	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

Grpmax group 0.00268% African / African-American · 2/74,646 alleles

Filtering AF 0.000445% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000125% 2/1,597,596 alleles · very rare exomes 0/1,445,472 · genomes 2/152,124 · joint denominator

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.Phe152Cys
Coding: c.455T>G
MANE Select: NM_000030
dbSNP: rs765812098
Type: single nucleotide variant
Location: chr2:240871380 (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 152: a UniProt-annotated variant site (in hp1; associated in cis with l-11 and m-340; results in protein destabilization; no loss of dimerization; decreased alanine--glyoxylate aminotransferase activity; loss of alanine--glyoxylate aminotransferase activity when associated with l-11 and m-340; mitochondrial mistargeting when associated with l-11 and m-340); a β-strand

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

Similar variants

AGXT p.Phe152Ile Pathogenic ★★ same residue
AGXT p.Phe152Ser Uncertain significance ★ ⚠ 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
AGXT c.525-1G>A Pathogenic ★★ same type
AGXT c.525-2A>T 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-phe152cys (accessed [today's date]).

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