Is AGXT2 p.Val428Phe (c.1282G>T) pathogenic?

AGXT2 p.Val428Phe (c.1282G>T) is classified Uncertain significance in AGXT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-11). AlphaMissense: likely benign (0.3224); Ultra-rare (popmax 0.0966%, amr).

How common is AGXT2 p.Val428Phe (c.1282G>T) in the general population?

AGXT2 p.Val428Phe (c.1282G>T) is ultra-rare (popmax 0.0966%, amr) (gnomAD).

What do computational predictors say about AGXT2 p.Val428Phe (c.1282G>T)?

AlphaMissense predicts likely benign (score 0.3224) — an in-silico prediction, not a clinical call.

AGXT2 p.Val428Phe

c.1282G>T · VCV3508143

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3224 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0966%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3224	likely benign
REVEL	0.632	indeterminate
SaProt	LLR -11.32	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 -1.3	GERP -3.1
Regional constraint	o/e 1.04	unconstrained · MANE · 49 kb · p 0.33 · regional, not allelic
Overall
CADD	19.08	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 0.0966% Admixed American · 58/60,026 alleles

Filtering AF 0.0767% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0696%

Overall 0.00372% 60/1,614,246 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0966%	1,035
Remaining individualsnot grpmax-eligible	0.0016%	62,510
European (non-Finnish)	8.47e-05%	1,180,036

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: AGXT2
Protein: p.Val428Phe
Coding: c.1282G>T
MANE Select: NM_031900
Type: single nucleotide variant
Location: chr5:35010056 (GRCh38)
Gene constraint: LOEUF 1.185 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.02

Full AGXT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AGXT2 p.Val428Ala Uncertain significance ★ ⚠ same residue
AGXT2 c.1188+1G>A Benign/Likely benign ★★ same type
AGXT2 p.Arg133Cys Benign ★★ same type
AGXT2 p.Arg242Gln Benign ★★ same type
AGXT2 p.Tyr203= Benign ★★ same type
AGXT2 p.Val116= Likely benign ★★ same type
AGXT2 p.Ala183Val Uncertain significance ★ ⚠ same type
AGXT2 p.Ala306Gly Uncertain significance ★ ⚠ 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/agxt2-p-val428phe (accessed [today's date]).

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