Is ATR p.Pro765Leu (c.2294C>T) pathogenic?

ATR p.Pro765Leu (c.2294C>T) is classified Uncertain significance in ATR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-16). AlphaMissense: likely benign (0.2245); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ATR p.Pro765Leu (c.2294C>T)?

ATR p.Pro765Leu (c.2294C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ATR p.Pro765Leu (c.2294C>T) in the general population?

ATR p.Pro765Leu (c.2294C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ATR p.Pro765Leu (c.2294C>T)?

AlphaMissense predicts likely benign (score 0.2245) — an in-silico prediction, not a clinical call.

ATR p.Pro765Leu

c.2294C>T · rs2108470513 · VCV1789150

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2245 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2245	likely benign
REVEL	0.273	benign-leaning
SaProt	LLR -8.05	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.9, phastCons 1
Overall
CADD	23.2	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

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.Pro765Leu
Coding: c.2294C>T
MANE Select: NM_032208 · reported on NM_001184
dbSNP: rs2108470513
Type: single nucleotide variant
Location: chr3:142555924 (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

ATR p.Pro765Thr Uncertain significance ★ ⚠ same residue
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

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-pro765leu (accessed [today's date]).

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