Is ATR p.Ser754= (c.2262A>G) pathogenic?

ATR p.Ser754= (c.2262A>G) is classified Likely benign in ATR (ClinVar, Single submitter, 1 submitter; last evaluated 2020-12-07). Very rare (popmax 0.0011%, sas); Associated with Inborn genetic diseases.

What condition is associated with ATR p.Ser754= (c.2262A>G)?

ATR p.Ser754= (c.2262A>G) is associated with Inborn genetic diseases (ClinVar).

How common is ATR p.Ser754= (c.2262A>G) in the general population?

ATR p.Ser754= (c.2262A>G) is very rare (popmax 0.0011%, sas) (gnomAD).

ATR p.Ser754=

c.2262A>G · rs1305280525 · VCV1788651

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.56	GERP -5.3, phastCons 0.071
Overall
CADD	7.905	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/90,936 alleles

Overall 6.84e-05% 1/1,461,448 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: ATR
Protein: p.Ser754=
Coding: c.2262A>G
MANE Select: NM_032208 · reported on NM_001184
dbSNP: rs1305280525
Type: single nucleotide variant
Location: chr3:142555956 (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.Ser754Leu Uncertain significance ★★ ⚠ same residue
ATR p.Ser754Ter Pathogenic ★ 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

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-ser754 (accessed [today's date]).

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