Is ATM p.Ser1455fs (c.4363del) pathogenic?

ATM p.Ser1455fs (c.4363del) is classified Pathogenic in ATM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-11-07). No gnomAD frequency available for this variant; Associated with hereditary neoplastic syndrome.

What condition is associated with ATM p.Ser1455fs (c.4363del)?

ATM p.Ser1455fs (c.4363del) is associated with hereditary neoplastic syndrome, ataxia telangiectasia (ClinVar).

How common is ATM p.Ser1455fs (c.4363del) in the general population?

ATM p.Ser1455fs (c.4363del) is no gnomAD frequency available for this variant (gnomAD).

ATM p.Ser1455fs

c.4363del · rs1591663478 · VCV824830

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 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 29 of 63
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.5, 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.Ser1455fs
Coding: c.4363del
MANE Select: NM_000051
dbSNP: rs1591663478
Type: Deletion
Location: chr11:108289724 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 1455: a UniProt-annotated variant site (in at); an α-helix; 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 neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ataxia telangiectasia

Similar variants

ATM p.Ser1455Asn Uncertain significance ★★ ⚠ same residue
ATM p.Ser1455Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
ATM p.Ser1455Thr Uncertain significance ★ ⚠ same residue
ATM p.Ser1455= 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-ser1455fs (accessed [today's date]).

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