Is ERCC2 p.Glu284fs (c.851del) pathogenic?

ERCC2 p.Glu284fs (c.851del) is classified Pathogenic in ERCC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-04). Absent from gnomAD; Associated with xeroderma pigmentosum group D.

What condition is associated with ERCC2 p.Glu284fs (c.851del)?

ERCC2 p.Glu284fs (c.851del) is associated with xeroderma pigmentosum group D (ClinVar).

How common is ERCC2 p.Glu284fs (c.851del) in the general population?

ERCC2 p.Glu284fs (c.851del) is absent from gnomAD (gnomAD).

ERCC2 p.Glu284fs

Q: How is Xeroderma pigmentosum-Cockayne syndrome complex inherited?

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

c.851del · rs2123288444 · VCV1685773

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

xeroderma pigmentosum group D

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 10 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.98	GERP 0.55, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ERCC2
Protein: p.Glu284fs
Coding: c.851del
MANE Select: NM_000400
dbSNP: rs2123288444
Type: Deletion
Location: chr19:45364084 (GRCh38)
Gene constraint: LOEUF 1.089 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.74 · 55 PDB
Residue 284: an α-helix

Full ERCC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

xeroderma pigmentosum group D — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Xeroderma pigmentosum-Cockayne syndrome complex (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ERCC2 c.2047-13_2048del Likely pathogenic ★★ same condition
ERCC2 c.594+2_594+5del Pathogenic/Likely pathogenic ★★ same condition
ERCC2 p.Arg196_Tyr197insTer Pathogenic ★★ same condition
ERCC2 p.Gln662fs Pathogenic/Likely pathogenic ★★ same condition
ERCC2 p.Phe568fs Pathogenic/Likely pathogenic ★★ same condition
ERCC2 p.Val714fs Pathogenic/Likely pathogenic ★★ same condition
ERCC2 p.Glu284Gln Uncertain significance ★★ ⚠ same residue
ERCC2 p.Glu284= Likely benign ★★ same residue

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/ercc2-p-glu284fs (accessed [today's date]).

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