Is ATE1 p.Pro194Ser (c.580C>T) pathogenic?

ATE1 p.Pro194Ser (c.580C>T) is classified Uncertain significance in ATE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-22). AlphaMissense: likely benign (0.1739); Very rare (popmax 0.00212%, nfe).

How common is ATE1 p.Pro194Ser (c.580C>T) in the general population?

ATE1 p.Pro194Ser (c.580C>T) is very rare (popmax 0.00212%, nfe) (gnomAD).

What do computational predictors say about ATE1 p.Pro194Ser (c.580C>T)?

AlphaMissense predicts likely benign (score 0.1739) — an in-silico prediction, not a clinical call.

ATE1 p.Pro194Ser

c.580C>T · rs747409744 · VCV3130779

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1739 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00212%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1739	likely benign
REVEL	0.218	benign-leaning
SaProt	LLR -5.99	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.64 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 91 kb · p 0.9 · regional, not allelic
Overall
CADD	26.4	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 0.00212% European (non-Finnish) · 25/1,179,832 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00155% 25/1,612,968 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.Pro194Ser
Coding: c.580C>T
MANE Select: NM_001001976
dbSNP: rs747409744
Type: single nucleotide variant
Location: chr10:121910909 (GRCh38)
Gene constraint: LOEUF 0.687 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.56 · 2 PDB
Residue 194: the 'disordered' region

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.Arg53Pro Uncertain significance ★ ⚠ same type
ATE1 p.Asn249Ile 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-pro194ser (accessed [today's date]).

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