Is ATM p.Phe172= (c.516C>T) pathogenic?

ATM p.Phe172= (c.516C>T) is classified Conflicting classifications of pathogenicity in ATM (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-12-16). No allele count reported in gnomAD v4.1 (AN 1,596,362); Associated with hereditary breast carcinoma.

What condition is associated with ATM p.Phe172= (c.516C>T)?

ATM p.Phe172= (c.516C>T) is associated with hereditary breast carcinoma, ataxia telangiectasia, hereditary neoplastic syndrome (ClinVar).

How common is ATM p.Phe172= (c.516C>T) in the general population?

ATM p.Phe172= (c.516C>T) is no allele count reported in gnomAD v4.1 (AN 1,596,362) (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.Phe172=

c.516C>T · rs1591499730 · VCV825499

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,596,362)

Conditions

hereditary breast carcinoma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.77 · evaluated, not missing
Pangolin	Δ0.44	gain · loss 0.40 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 0.55	GERP -0.89, phastCons 0.77
Overall
CADD	11.93	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,596,362). 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.Phe172=
Coding: c.516C>T
MANE Select: NM_000051
dbSNP: rs1591499730
Type: single nucleotide variant
Location: chr11:108243972 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 172: 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

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.Phe172Leu Uncertain significance ★★ same residue
ATM p.Phe172Cys Uncertain significance ★ ⚠ same residue
ATM p.Phe172Val Uncertain significance ★ ⚠ same residue
ATM p.Phe172fs 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
ATM c.3078-1G>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-phe172 (accessed [today's date]).

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