Is AGXT p.Ile119Val (c.355A>G) pathogenic?

AGXT p.Ile119Val (c.355A>G) is classified Uncertain significance in AGXT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-31). AlphaMissense: likely benign (0.0964); Very rare (popmax 0.000429%, nfe).

How common is AGXT p.Ile119Val (c.355A>G) in the general population?

AGXT p.Ile119Val (c.355A>G) is very rare (popmax 0.000429%, nfe) (gnomAD).

What do computational predictors say about AGXT p.Ile119Val (c.355A>G)?

AlphaMissense predicts likely benign (score 0.0964) — an in-silico prediction, not a clinical call.

AGXT p.Ile119Val

c.355A>G · rs2106427685 · VCV1677853

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0964 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000429%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0964	likely benign
REVEL	0.447	indeterminate
SaProt	LLR -5.95	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.25	donor gain · deltas
Constraint at this position
Conservation	phyloP 0.74	GERP -2.5, phastCons 0.008
Regional constraint	o/e 1.00	unconstrained · MANE · 9,952 bp · p 0.92 · regional, not allelic
Overall
CADD	11.75	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000429% European (non-Finnish) · 5/1,166,820 alleles

Filtering AF 0.000126% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.1e-05%

Overall 0.000417% 6/1,437,376 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00162%	61,628
European (non-Finnish)grpmax	0.000429%	233,364

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ile119Val
Coding: c.355A>G
MANE Select: NM_000030
dbSNP: rs2106427685
Type: single nucleotide variant
Location: chr2:240869359 (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 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
AGXT c.595+1G>T Pathogenic ★★ same type
AGXT c.596-2A>G 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-ile119val (accessed [today's date]).

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