Is AGXT p.Pro11Ser (c.31C>T) pathogenic?

AGXT p.Pro11Ser (c.31C>T) is classified Uncertain significance in AGXT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-10-19). AlphaMissense: likely benign (0.2941); Ultra-rare (popmax 0.0167%, amr); Associated with alanine glyoxylate aminotransferase deficiency.

What condition is associated with AGXT p.Pro11Ser (c.31C>T)?

AGXT p.Pro11Ser (c.31C>T) is associated with alanine glyoxylate aminotransferase deficiency (ClinVar).

How common is AGXT p.Pro11Ser (c.31C>T) in the general population?

AGXT p.Pro11Ser (c.31C>T) is ultra-rare (popmax 0.0167%, amr) (gnomAD).

What do computational predictors say about AGXT p.Pro11Ser (c.31C>T)?

AlphaMissense predicts likely benign (score 0.2941) — an in-silico prediction, not a clinical call.

AGXT p.Pro11Ser

c.31C>T · rs375712696 · VCV2069242

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2941 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

alanine glyoxylate aminotransferase deficiency

Computational evidence

Protein change
AlphaMissense	0.2941	likely benign
REVEL	0.515	indeterminate
SaProt	LLR -10.46	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 1.3, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 9,952 bp · p 0.92 · regional, not allelic
Overall
CADD	23.1	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 0.0167% Admixed American · 10/59,994 alleles

Filtering AF 0.009% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00681%

Overall 0.00403% 65/1,612,982 alleles · ultra-rare exomes 61/1,460,742 · genomes 4/152,240 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0167%	5,999
Middle Eastern	0.0164%	6,082
Remaining individualsnot grpmax-eligible	0.008%	12,493
South Asian	0.00659%	15,174
European (non-Finnish)	0.00356%	28,093
African / African-American	0.00133%	74,940

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.Pro11Ser
Coding: c.31C>T
MANE Select: NM_000030
dbSNP: rs375712696
Type: single nucleotide variant
Location: chr2:240868896 (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 11: an α-helix; a UniProt-annotated variant site (in allele minor; associated in cis with m-340; decreased specific alanine--glyoxylate aminotransferase activity in vitro when associated with m-340; loss of alanine--glyoxylate aminotransferase activity in vitro when associated with i-152 and m-340; loss of alanine--glyoxylate aminotransferase activity in vitro when associated with r-170 and m-340; loss of alanine--glyoxylate aminotransferase activity in vitro when associated with t-244 and m-340; causes mitochondrial mistargeting when associated with r-170 and m-340)

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

Disease context

alanine glyoxylate aminotransferase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AGXT p.Pro11His Conflicting classifications of pathogenicity ★ same residue
AGXT p.Pro11Ala Uncertain significance ★★ ⚠ same residue
AGXT p.Pro11Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
AGXT p.Pro11= Likely benign ★ same residue
AGXT p.Pro11fs Likely pathogenic ★ same residue
AGXT p.Arg289His Conflicting classifications of pathogenicity ★ ⚠ same condition
AGXT p.Arg381Lys Conflicting classifications of pathogenicity ★ ⚠ same condition
AGXT p.Pro11Leu Likely benign ★ same residue

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-pro11ser (accessed [today's date]).

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