Is ATR p.Trp1494Arg (c.4480T>C) pathogenic?

ATR p.Trp1494Arg (c.4480T>C) is classified Uncertain significance in ATR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-12). AlphaMissense: likely pathogenic (0.9992); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ATR p.Trp1494Arg (c.4480T>C)?

ATR p.Trp1494Arg (c.4480T>C) is associated with Inborn genetic diseases (ClinVar).

How common is ATR p.Trp1494Arg (c.4480T>C) in the general population?

ATR p.Trp1494Arg (c.4480T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ATR p.Trp1494Arg (c.4480T>C)?

AlphaMissense predicts likely pathogenic (score 0.9992) — an in-silico prediction, not a clinical call.

ATR p.Trp1494Arg

c.4480T>C · rs2473231953 · VCV3221164

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9992 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9992	likely pathogenic · top 2% in ATR
REVEL	0.798	moderately pathogenic-leaning
SaProt	LLR -10.74	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 11	GERP 2.7, phastCons 1
Overall
CADD	26.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ATR
Protein: p.Trp1494Arg
Coding: c.4480T>C
MANE Select: NM_001184
dbSNP: rs2473231953
Type: single nucleotide variant
Location: chr3:142515418 (GRCh38)
Structure: AlphaFold pLDDT 72.76 · 5 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ANTXR1 p.Ala26Val Uncertain significance ★★ ⚠ same condition
ANTXR1 p.Arg444Gln Uncertain significance ★★ ⚠ same condition
ANTXR1 p.Arg557Cys Uncertain significance ★★ ⚠ same condition
ANTXR1 p.Gly369Ser Uncertain significance ★★ ⚠ same condition
ANTXR1 p.Leu45Val Uncertain significance ★★ ⚠ same condition
ANTXR1 p.Pro524Leu Uncertain significance ★★ ⚠ same condition
ANTXR1 p.Pro534Gln Uncertain significance ★★ ⚠ same condition
ANTXR1 p.Thr503Asn Uncertain significance ★★ ⚠ same condition

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/atr-p-trp1494arg (accessed [today's date]).

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