Is ATM p.Pro2056= (c.6168C>G) pathogenic?

ATM p.Pro2056= (c.6168C>G) is classified Likely benign in ATM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-14). Ultra-rare (popmax 0.0165%, mid); Associated with ataxia telangiectasia.

What condition is associated with ATM p.Pro2056= (c.6168C>G)?

ATM p.Pro2056= (c.6168C>G) is associated with ataxia telangiectasia (ClinVar).

How common is ATM p.Pro2056= (c.6168C>G) in the general population?

ATM p.Pro2056= (c.6168C>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

How is Ataxia-telangiectasia inherited?

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

ATM p.Pro2056=

c.6168C>G · rs1057520449 · VCV2001474

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

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 -1	GERP -4.8
Overall
CADD	0.653	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Overall 6.2e-05% 1/1,614,120 alleles · ultra-rare exomes 1/1,461,830 · genomes 0/152,290 · joint denominator

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.Pro2056=
Coding: c.6168C>G
MANE Select: NM_000051
dbSNP: rs1057520449
Type: single nucleotide variant
Location: chr11:108316083 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 2056: 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.Pro2056Leu Uncertain significance ★★ ⚠ same residue
ATM p.Pro2056Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
ATM p.Pro2056Thr 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-pro2056 (accessed [today's date]).

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