Is ATM p.Phe1234= (c.3702T>C) pathogenic?

ATM p.Phe1234= (c.3702T>C) is classified Benign/Likely benign in ATM (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-12-06). Very rare (popmax 8.99e-05%, nfe); Associated with hereditary breast carcinoma.

What condition is associated with ATM p.Phe1234= (c.3702T>C)?

ATM p.Phe1234= (c.3702T>C) is associated with hereditary breast carcinoma, ataxia telangiectasia, hereditary neoplastic syndrome (ClinVar).

How common is ATM p.Phe1234= (c.3702T>C) in the general population?

ATM p.Phe1234= (c.3702T>C) is very rare (popmax 8.99e-05%, nfe) (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.Phe1234=

c.3702T>C · rs876659605 · VCV1734115

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 8.99e-05%, nfe)

Conditions

hereditary breast carcinoma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -0.46, phastCons 1
Overall
CADD	8.254	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.99e-05% European (non-Finnish) · 1/1,112,248 alleles

Overall 7.22e-05% 1/1,384,192 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.Phe1234=
Coding: c.3702T>C
MANE Select: NM_000051
dbSNP: rs876659605
Type: single nucleotide variant
Location: chr11:108282835 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 1234: a UniProt-annotated variant site (in at); a UniProt-annotated variant site (in at; uncertain significance); a UniProt-annotated variant site (in at; uncertain significance; increases protein abundance)

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 hereditary neoplastic syndrome

For Hereditary breast cancer (Orphanet):

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

Similar variants

ATM p.Phe1234Leu Uncertain significance ★★ same residue
ATM c.1607+1G>T Pathogenic ★★★ same condition
ATM c.2251-4A>G Likely pathogenic ★★★ same condition
ATM c.2466+5G>C Likely pathogenic ★★★ same condition
ATM c.3078-1G>A Pathogenic ★★★ same condition
ATM c.332-1G>A Pathogenic ★★★ same condition
ATM c.4909+1G>A Pathogenic ★★★ same condition
ATM c.496+5G>A 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-phe1234 (accessed [today's date]).

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