Is ATM p.Pro2775= (c.8325C>T) pathogenic?

ATM p.Pro2775= (c.8325C>T) is classified Benign/Likely benign in ATM (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-03-04). Absent from gnomAD v4.1; Associated with hereditary breast carcinoma.

What condition is associated with ATM p.Pro2775= (c.8325C>T)?

ATM p.Pro2775= (c.8325C>T) is associated with hereditary breast carcinoma, ataxia telangiectasia, hereditary neoplastic syndrome (ClinVar).

How common is ATM p.Pro2775= (c.8325C>T) in the general population?

ATM p.Pro2775= (c.8325C>T) is absent from gnomAD v4.1 (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.Pro2775=

c.8325C>T · rs2547416737 · VCV1762939

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 0.2	GERP -4.2, phastCons 0.99
Overall
CADD	5.908	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ATM
Protein: p.Pro2775=
Coding: c.8325C>T
MANE Select: NM_000051
dbSNP: rs2547416737
Type: single nucleotide variant
Location: chr11:108343278 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 2775: a UniProt-annotated variant site (in at; uncertain significance; reduces protein abundance); a UniProt-annotated variant site (in at); the pi3k/pi4k catalytic domain; a UniProt-annotated variant site (in at; uncertain significance); a β-strand; 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.Pro2775Leu Uncertain significance ★★ ⚠ same residue
ATM p.Pro2775Ser Uncertain significance ★★ ⚠ same residue
ATM p.Pro2775Ala Uncertain significance ★ same residue
ATM p.Pro2775Arg Uncertain significance ★ ⚠ same residue
ATM p.Pro2775fs Pathogenic ★★ 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

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-pro2775 (accessed [today's date]).

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