Is ATM p.Arg447fs (c.1340del) pathogenic?

ATM p.Arg447fs (c.1340del) is classified Pathogenic in ATM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-05). Associated with hereditary neoplastic syndrome.

What condition is associated with ATM p.Arg447fs (c.1340del)?

ATM p.Arg447fs (c.1340del) is associated with hereditary neoplastic syndrome (ClinVar).

ATM p.Arg447fs

c.1340del · VCV3802736

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 10 of 63
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.9	GERP 2.7, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: ATM
Protein: p.Arg447fs
Coding: c.1340del
MANE Select: NM_000051
Type: Deletion
Location: chr11:108250805 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 447: a UniProt-annotated variant site (in at); a β-strand; a UniProt-annotated variant site (in at; uncertain significance)

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ATM p.Arg447Ter Pathogenic ★★ same residue
ATM p.Arg447Leu Uncertain significance ★★ same residue
ATM p.Arg447Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
ATM c.2639-22_2639-20del Pathogenic ★★★ same condition
ATM p.Asn1719fs Pathogenic ★★★ same condition
ATM p.Asp130fs Pathogenic ★★★ same condition
ATM p.Glu1267_Val1268insTer Pathogenic ★★★ same condition
ATM p.Leu1764fs Pathogenic ★★★ 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/atm-p-arg447fs (accessed [today's date]).

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