Is ATM p.Val682fs (c.2044_2057del) pathogenic?

ATM p.Val682fs (c.20442057del) is classified Pathogenic in ATM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-11). Absent from gnomAD; Associated with hereditary breast carcinoma.

What condition is associated with ATM p.Val682fs (c.2044_2057del)?

ATM p.Val682fs (c.2044_2057del) is associated with hereditary breast carcinoma, ataxia telangiectasia (ClinVar).

How common is ATM p.Val682fs (c.2044_2057del) in the general population?

ATM p.Val682fs (c.2044_2057del) is absent from gnomAD (gnomAD).

How is Hereditary breast cancer inherited?

Typically Autosomal dominant, Multigenic/multifactorial (Orphanet). A genetic counselor can assess individual risk for a family.

ATM p.Val682fs

c.2044_2057del · rs2135369731 · VCV1071666

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary breast carcinoma

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 13 of 63
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.7	GERP -1.2, 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.Val682fs
Coding: c.2044_2057del
MANE Select: NM_000051
dbSNP: rs2135369731
Type: Deletion
Location: chr11:108253956 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 682: a UniProt-annotated variant site (in at); 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 breast carcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ataxia telangiectasia

For Hereditary breast cancer (Orphanet):

Inheritance: Autosomal dominant, Multigenic/multifactorial
Onset: Adult, Elderly

Similar variants

ATM p.Val682Gly Uncertain significance ★★ same residue
ATM p.Val682Leu Uncertain significance ★★ ⚠ same residue
ATM p.Val682Phe Uncertain significance ★★ same residue
ATM p.Val682= 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
ATM p.Asp130fs 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-val682fs (accessed [today's date]).

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