Is MRE11 p.Glu645= (c.1935G>A) pathogenic?

MRE11 p.Glu645= (c.1935G>A) is classified Likely benign in MRE11 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-19). Absent from gnomAD v4.1; Associated with ataxia-telangiectasia-like disorder.

What condition is associated with MRE11 p.Glu645= (c.1935G>A)?

MRE11 p.Glu645= (c.1935G>A) is associated with ataxia-telangiectasia-like disorder, hereditary neoplastic syndrome (ClinVar).

How common is MRE11 p.Glu645= (c.1935G>A) in the general population?

MRE11 p.Glu645= (c.1935G>A) is absent from gnomAD v4.1 (gnomAD).

MRE11 p.Glu645=

c.1935G>A · rs1060504338 · VCV414696

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

ataxia-telangiectasia-like disorder

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 -0.37	GERP -3.1, phastCons 0.058
Overall
CADD	5.79	PHRED · no single calibrated threshold — expert panels disagree

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: MRE11
Protein: p.Glu645=
Coding: c.1935G>A
MANE Select: NM_005591
dbSNP: rs1060504338
Type: single nucleotide variant
Location: chr11:94435891 (GRCh38)
Gene constraint: LOEUF 0.801 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 76.05 · 10 PDB
Residue 645: a UniProt-annotated variant site (in atld1)

Full MRE11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Also linked: hereditary neoplastic syndrome

Similar variants

MRE11 p.Glu645Lys Uncertain significance ★ ⚠ same residue
MRE11 c.1098+2T>C Likely pathogenic ★★ same condition
MRE11 c.1225+2T>C Pathogenic/Likely pathogenic ★★ same condition
MRE11 c.1326+2T>G Likely pathogenic ★★ same condition
MRE11 c.1327-2A>G Likely pathogenic ★★ same condition
MRE11 c.1783+1G>A Likely pathogenic ★★ same condition
MRE11 c.1867+2T>C Pathogenic/Likely pathogenic ★★ same condition
MRE11 c.1927-1G>T 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/mre11-p-glu645 (accessed [today's date]).

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