Is ATE1 p.Val498Phe (c.1492G>T) pathogenic?

ATE1 p.Val498Phe (c.1492G>T) is classified Uncertain significance in ATE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-30). AlphaMissense: ambiguous (0.5288); Very rare (popmax 0.00223%, eas).

How common is ATE1 p.Val498Phe (c.1492G>T) in the general population?

ATE1 p.Val498Phe (c.1492G>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about ATE1 p.Val498Phe (c.1492G>T)?

AlphaMissense predicts ambiguous (score 0.5288) — an in-silico prediction, not a clinical call.

ATE1 p.Val498Phe

c.1492G>T · rs958173314 · VCV3130775

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5288 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Computational evidence

Protein change
AlphaMissense	0.5288	ambiguous
REVEL	0.506	indeterminate
SaProt	LLR -9.93	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 0.8, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 47 kb · p 0.71 · regional, not allelic
Overall
CADD	24.5	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 0.00223% East Asian · 1/44,872 alleles

Overall 6.84e-05% 1/1,461,876 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: ATE1
Protein: p.Val498Phe
Coding: c.1492G>T
MANE Select: NM_001001976
dbSNP: rs958173314
Type: single nucleotide variant
Location: chr10:121743745 (GRCh38)
Gene constraint: LOEUF 0.687 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.56 · 2 PDB
Residue 498: an α-helix

Full ATE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATE1 p.Val498Ile Uncertain significance ★ ⚠ same residue
ATE1 p.Ala123Thr Uncertain significance ★ ⚠ same type
ATE1 p.Ala125Val Uncertain significance ★ ⚠ same type
ATE1 p.Ala246Pro Uncertain significance ★ ⚠ same type
ATE1 p.Ala326Thr Uncertain significance ★ ⚠ same type
ATE1 p.Arg297His Uncertain significance ★ ⚠ same type
ATE1 p.Arg317Gly Uncertain significance ★ ⚠ same type
ATE1 p.Arg53Pro 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/ate1-p-val498phe (accessed [today's date]).

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