Is ATM p.Trp1461Ter (c.4382G>A) pathogenic?

ATM p.Trp1461Ter (c.4382G>A) is classified Pathogenic in ATM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-25). Absent from gnomAD v4.1; Associated with ataxia telangiectasia.

What condition is associated with ATM p.Trp1461Ter (c.4382G>A)?

ATM p.Trp1461Ter (c.4382G>A) is associated with ataxia telangiectasia (ClinVar).

How common is ATM p.Trp1461Ter (c.4382G>A) in the general population?

ATM p.Trp1461Ter (c.4382G>A) is absent from gnomAD v4.1 (gnomAD).

How is Ataxia-telangiectasia inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ATM p.Trp1461Ter

c.4382G>A · VCV4729223

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

ataxia telangiectasia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 29 of 63
REVEL	0.237	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.6	GERP 2.5, phastCons 1
Overall
CADD	38.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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.Trp1461Ter
Coding: c.4382G>A
MANE Select: NM_000051
Type: single nucleotide variant
Location: chr11:108289747 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 1461: 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

ataxia telangiectasia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Ataxia-telangiectasia (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy
Prevalence: 1-5 / 10 000 (Norway)

Similar variants

ATM p.Trp1461Leu Uncertain significance ★ same residue
ATM p.Trp1461Arg Uncertain significance ★ ⚠ same residue
ATM p.Trp1461Gly 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

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-trp1461ter (accessed [today's date]).

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