Is ATM p.Pro2015Ala (c.6043C>G) pathogenic?

ATM p.Pro2015Ala (c.6043C>G) is classified Uncertain significance in ATM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-26). AlphaMissense: likely benign (0.3291); Absent from gnomAD v4.1; Associated with ataxia telangiectasia.

What condition is associated with ATM p.Pro2015Ala (c.6043C>G)?

ATM p.Pro2015Ala (c.6043C>G) is associated with ataxia telangiectasia (ClinVar).

How common is ATM p.Pro2015Ala (c.6043C>G) in the general population?

ATM p.Pro2015Ala (c.6043C>G) 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.

What do computational predictors say about ATM p.Pro2015Ala (c.6043C>G)?

AlphaMissense predicts likely benign (score 0.3291) — an in-silico prediction, not a clinical call.

ATM p.Pro2015Ala

c.6043C>G · rs2136119293 · VCV2814786

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3291 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

ataxia telangiectasia

Computational evidence

Protein change
AlphaMissense	0.3291	likely benign
REVEL	0.527	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.4, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 60 kb · p 6.4e-07 · regional, not allelic
Overall
CADD	25.7	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.Pro2015Ala
Coding: c.6043C>G
MANE Select: NM_000051
dbSNP: rs2136119293
Type: single nucleotide variant
Location: chr11:108315859 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 2015: 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); 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.Pro2015Leu Uncertain significance ★ same residue
ATM p.Pro2015Ser 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
ATM c.4909+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-pro2015ala (accessed [today's date]).

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