Is ATM p.Asp2448Glu (c.7344T>A) pathogenic?

ATM p.Asp2448Glu (c.7344T>A) is classified Uncertain significance in ATM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-03-04). AlphaMissense: likely pathogenic (0.8766); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with ATM p.Asp2448Glu (c.7344T>A)?

ATM p.Asp2448Glu (c.7344T>A) is associated with hereditary neoplastic syndrome (ClinVar).

How common is ATM p.Asp2448Glu (c.7344T>A) in the general population?

ATM p.Asp2448Glu (c.7344T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ATM p.Asp2448Glu (c.7344T>A)?

AlphaMissense predicts likely pathogenic (score 0.8766) — an in-silico prediction, not a clinical call.

ATM p.Asp2448Glu

c.7344T>A · rs2547261012 · VCV2136236

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8766 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.8766	likely pathogenic · top 9% in ATM
REVEL	0.616	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP -0.91, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 60 kb · p 6.4e-07 · regional, not allelic
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

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.Asp2448Glu
Coding: c.7344T>A
MANE Select: NM_000051
dbSNP: rs2547261012
Type: single nucleotide variant
Location: chr11:108330250 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 2448: a UniProt-annotated variant site (in at; uncertain significance; reduces protein abundance); a UniProt-annotated variant site (in at); the fat domain; a UniProt-annotated variant site (in at; uncertain significance); an α-helix; 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

Similar variants

ATM p.Asp2448Asn Uncertain significance ★★ ⚠ same residue
ATM p.Asp2448Gly Uncertain significance ★★ ⚠ same residue
ATM p.Asp2448His Uncertain significance ★★ ⚠ same residue
ATM p.Asp2448Val Uncertain significance ★★ ⚠ same residue
ATM p.Asp2448Tyr 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

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-asp2448glu (accessed [today's date]).

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