Is ATM p.Ala463= (c.1389A>C) pathogenic?

ATM p.Ala463= (c.1389A>C) is classified Likely benign in ATM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-08). Very rare (popmax 0.00329%, sas); Associated with ataxia telangiectasia.

What condition is associated with ATM p.Ala463= (c.1389A>C)?

ATM p.Ala463= (c.1389A>C) is associated with ataxia telangiectasia, hereditary neoplastic syndrome (ClinVar).

How common is ATM p.Ala463= (c.1389A>C) in the general population?

ATM p.Ala463= (c.1389A>C) is very rare (popmax 0.00329%, sas) (gnomAD).

How is Ataxia-telangiectasia inherited?

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

ATM p.Ala463=

c.1389A>C · VCV4757441

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Conditions

ataxia telangiectasia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.52	GERP -5.1
Overall
CADD	7.054	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,082 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000205% 3/1,461,870 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ATM
Protein: p.Ala463=
Coding: c.1389A>C
MANE Select: NM_000051
Type: single nucleotide variant
Location: chr11:108250854 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 463: a UniProt-annotated variant site (in at); an α-helix; a UniProt-annotated variant site (in at; uncertain significance)

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

Also linked: hereditary neoplastic syndrome

For Ataxia-telangiectasia (Orphanet):

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

Similar variants

ATM p.Ala463Thr Uncertain significance ★★ same residue
ATM p.Ala463Gly Uncertain significance ★ same residue
ATM p.Ala463Glu 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-ala463 (accessed [today's date]).

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