Is ATR p.Ser464= (c.1392T>C) pathogenic?

ATR p.Ser464= (c.1392T>C) is classified Likely benign in ATR (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-05). Very rare (popmax 0.000593%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ATR p.Ser464= (c.1392T>C)?

ATR p.Ser464= (c.1392T>C) is associated with Inborn genetic diseases (ClinVar).

How common is ATR p.Ser464= (c.1392T>C) in the general population?

ATR p.Ser464= (c.1392T>C) is very rare (popmax 0.000593%, nfe) (gnomAD).

ATR p.Ser464=

c.1392T>C · rs757472802 · VCV2561350

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.8	GERP 0.048, phastCons 0.32
Overall
CADD	9.822	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000593% European (non-Finnish) · 7/1,179,644 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000479% 7/1,461,354 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.Ser464=
Coding: c.1392T>C
MANE Select: NM_032208 · reported on NM_001184
dbSNP: rs757472802
Type: single nucleotide variant
Location: chr3:142560412 (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.Gly464= 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-ser464 (accessed [today's date]).

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