Is ATE1 p.Arg53Pro (c.158G>C) pathogenic?

ATE1 p.Arg53Pro (c.158G>C) is classified Uncertain significance in ATE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-15). AlphaMissense: likely pathogenic (0.9996); Very rare (popmax 0.005%, amr).

How common is ATE1 p.Arg53Pro (c.158G>C) in the general population?

ATE1 p.Arg53Pro (c.158G>C) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about ATE1 p.Arg53Pro (c.158G>C)?

AlphaMissense predicts likely pathogenic (score 0.9996) — an in-silico prediction, not a clinical call.

ATE1 p.Arg53Pro

c.158G>C · VCV4161673

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9996 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9996	likely pathogenic · top 1% in ATE1
REVEL	0.43	indeterminate
SaProt	LLR -17.11	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.37 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 1.1, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 91 kb · p 0.9 · regional, not allelic
Overall
CADD	31.0	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 0.005% Admixed American · 3/60,020 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000205% 3/1,461,676 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.Arg53Pro
Coding: c.158G>C
MANE Select: NM_001001976
Type: single nucleotide variant
Location: chr10:121924278 (GRCh38)
Gene constraint: LOEUF 0.687 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.56 · 2 PDB
Residue 53: a turn

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

Similar variants

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.Asn249Ile Uncertain significance ★ ⚠ same type
ATE1 p.Asp122Glu 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-arg53pro (accessed [today's date]).

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