Is ATR p.Ser1822Pro (c.5464T>C) pathogenic?

ATR p.Ser1822Pro (c.5464T>C) is classified Uncertain significance in ATR (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-04). AlphaMissense: likely pathogenic (0.729); Very rare (popmax 0.000169%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ATR p.Ser1822Pro (c.5464T>C)?

ATR p.Ser1822Pro (c.5464T>C) is associated with Inborn genetic diseases (ClinVar).

How common is ATR p.Ser1822Pro (c.5464T>C) in the general population?

ATR p.Ser1822Pro (c.5464T>C) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about ATR p.Ser1822Pro (c.5464T>C)?

AlphaMissense predicts likely pathogenic (score 0.729) — an in-silico prediction, not a clinical call.

ATR p.Ser1822Pro

c.5464T>C · rs1299303517 · VCV1747687

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.729 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.729	likely pathogenic
REVEL	0.165	moderately benign-leaning
SaProt	LLR -13.48	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.2, phastCons 1
Overall
CADD	23.6	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 0.000169% European (non-Finnish) · 2/1,179,964 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,930 alleles · very rare exomes 1/1,461,766 · genomes 1/152,164 · joint denominator

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: ATR
Protein: p.Ser1822Pro
Coding: c.5464T>C
MANE Select: NM_001184
dbSNP: rs1299303517
Type: single nucleotide variant
Location: chr3:142498691 (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.Ser1822= Likely benign ★ 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-ser1822pro (accessed [today's date]).

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