Is AGXT p.Val102Phe (c.304G>T) pathogenic?

AGXT p.Val102Phe (c.304G>T) is classified Uncertain significance in AGXT (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-24). AlphaMissense: likely pathogenic (0.591); Very rare (popmax 0.00133%, afr).

How common is AGXT p.Val102Phe (c.304G>T) in the general population?

AGXT p.Val102Phe (c.304G>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about AGXT p.Val102Phe (c.304G>T)?

AlphaMissense predicts likely pathogenic (score 0.591) — an in-silico prediction, not a clinical call.

AGXT p.Val102Phe

c.304G>T · rs2058978746 · VCV969010

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.591 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.591	likely pathogenic
REVEL	0.776	moderately pathogenic-leaning
SaProt	LLR -13.75	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 1.3, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 9,952 bp · p 0.92 · regional, not allelic
Overall
CADD	25.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00133% African / African-American · 1/75,054 alleles

Overall 6.85e-05% 1/1,460,124 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.Val102Phe
Coding: c.304G>T
MANE Select: NM_000030
dbSNP: rs2058978746
Type: single nucleotide variant
Location: chr2:240869308 (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 102: a β-strand

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

Similar variants

AGXT p.Val102Asp Likely pathogenic ★ same residue
AGXT p.Val102= Uncertain significance same residue
AGXT p.Val102_Gly103insValLeuVal 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
AGXT c.525-1G>A 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-val102phe (accessed [today's date]).

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