Is ATM p.Phe172fs (c.516_517delinsG) pathogenic?

ATM p.Phe172fs (c.516517delinsG) is classified Pathogenic in ATM (ClinVar, Single submitter, 1 submitter; last evaluated 2020-12-11). Absent from gnomAD; Associated with hereditary neoplastic syndrome.

What condition is associated with ATM p.Phe172fs (c.516_517delinsG)?

ATM p.Phe172fs (c.516_517delinsG) is associated with hereditary neoplastic syndrome (ClinVar).

How common is ATM p.Phe172fs (c.516_517delinsG) in the general population?

ATM p.Phe172fs (c.516_517delinsG) is absent from gnomAD (gnomAD).

ATM p.Phe172fs

c.516_517delinsG · rs2497129132 · VCV1745722

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

hereditary neoplastic syndrome

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 6 of 63
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.55	GERP -0.89, phastCons 0.77

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.Phe172fs
Coding: c.516_517delinsG
MANE Select: NM_000051
dbSNP: rs2497129132
Type: Indel
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 neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ATM p.Phe172Leu Uncertain significance ★★ same residue
ATM p.Phe172= Conflicting classifications of pathogenicity ★ same residue
ATM p.His1082fs Pathogenic ★★★ same condition
ATM p.Phe1877fs Pathogenic ★★★ same condition
ATM p.Ser2855_Val2856delinsArgIle Pathogenic ★★★ same condition
ATM p.Arg1466Pro Uncertain significance ★★★ same condition
ATM c.2125-16_2128delinsCAAATTTATATT Likely pathogenic ★★ same condition
ATM c.2839-3_2839delinsGATACTA Pathogenic/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-phe172fs (accessed [today's date]).

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