Is ATM p.Leu165fs (c.492dup) pathogenic?

ATM p.Leu165fs (c.492dup) is classified Pathogenic in ATM (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-17). Absent from gnomAD; Associated with ataxia telangiectasia.

What condition is associated with ATM p.Leu165fs (c.492dup)?

ATM p.Leu165fs (c.492dup) is associated with ataxia telangiectasia (ClinVar).

How common is ATM p.Leu165fs (c.492dup) in the general population?

ATM p.Leu165fs (c.492dup) is absent from gnomAD (gnomAD).

How is Ataxia-telangiectasia inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ATM p.Leu165fs

c.492dup · rs1555059513 · VCV453547

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

ataxia telangiectasia

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 5 of 63
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 2.7, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ATM
Protein: p.Leu165fs
Coding: c.492dup
MANE Select: NM_000051
dbSNP: rs1555059513
Type: Duplication
Location: chr11:108235828 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 165: a UniProt-annotated variant site (in at); an α-helix

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

Disease context

ataxia telangiectasia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Ataxia-telangiectasia (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy
Prevalence: 1-5 / 10 000 (Norway)

Similar variants

ATM p.Leu165= Benign/Likely benign ★★ same residue
ATM p.Leu165Ter Pathogenic ★ same residue
ATM p.Leu165Ile Uncertain significance ★ ⚠ same residue
ATM p.Leu165Val Uncertain significance ★ ⚠ same residue
ATM c.6997dup Pathogenic ★★★ same condition
ATM p.Cys718fs Pathogenic ★★★ same condition
ATM p.Ser837fs Pathogenic ★★★ same condition
ATM c.2921+2dup Likely 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-leu165fs (accessed [today's date]).

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