Is ATM p.Pro1069fs (c.3206del) pathogenic?

ATM p.Pro1069fs (c.3206del) is classified Pathogenic/Likely pathogenic in ATM (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-01-08). Very rare (popmax 0.000169%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with ATM p.Pro1069fs (c.3206del)?

ATM p.Pro1069fs (c.3206del) is associated with hereditary neoplastic syndrome, ataxia telangiectasia, hereditary breast carcinoma (ClinVar).

How common is ATM p.Pro1069fs (c.3206del) in the general population?

ATM p.Pro1069fs (c.3206del) is very rare (popmax 0.000169%, nfe) (gnomAD).

ATM p.Pro1069fs

c.3206del · rs1060501677 · VCV407680

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

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 22 of 63
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.99	GERP -5.4

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,179,990 alleles

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

Overall 0.000137% 2/1,461,788 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: ATM
Protein: p.Pro1069fs
Coding: c.3206del
MANE Select: NM_000051
dbSNP: rs1060501677
Type: Deletion
Location: chr11:108272773 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 1069: 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

Also linked: ataxia telangiectasia hereditary breast carcinoma

Similar variants

ATM p.Pro1069Ala Uncertain significance ★★ ⚠ same residue
ATM p.Pro1069Leu Uncertain significance ★ same residue
ATM p.Pro1069Thr Uncertain significance ★ ⚠ same residue
ATM p.Pro1069= Likely benign ★ same residue
ATM p.Pro1069Ser Likely benign ★ same residue
ATM c.2639-22_2639-20del Pathogenic ★★★ same condition
ATM p.Ala2045_Leu2046insTer Pathogenic ★★★ same condition
ATM p.Asn1719fs 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-pro1069fs (accessed [today's date]).

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