Is ERCC2 p.Arg616fs (c.1847_1850del) pathogenic?

ERCC2 p.Arg616fs (c.18471850del) is classified Pathogenic/Likely pathogenic in ERCC2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-17). Absent from gnomAD; Associated with cerebrooculofacioskeletal syndrome 2.

What condition is associated with ERCC2 p.Arg616fs (c.1847_1850del)?

ERCC2 p.Arg616fs (c.1847_1850del) is associated with cerebrooculofacioskeletal syndrome 2, xeroderma pigmentosum group D, trichothiodystrophy 1, photosensitive (ClinVar).

How common is ERCC2 p.Arg616fs (c.1847_1850del) in the general population?

ERCC2 p.Arg616fs (c.1847_1850del) is absent from gnomAD (gnomAD).

ERCC2 p.Arg616fs

c.1847_1850del · rs2514000268 · VCV3023764

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

cerebrooculofacioskeletal syndrome 2

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 20 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -7.4	GERP -3.3

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.Arg616fs
Coding: c.1847_1850del
MANE Select: NM_000400
dbSNP: rs2514000268
Type: Microsatellite
Location: chr19:45352798 (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 616: the 'mediates interaction with mms19' region; a UniProt-annotated variant site (sequence variant); a UniProt-annotated variant site (in xp-d and ttd1); a UniProt-annotated variant site (in xp-d and cofs2)

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

Disease context

cerebrooculofacioskeletal syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: xeroderma pigmentosum group D trichothiodystrophy 1, photosensitive

Similar variants

ERCC2 p.Arg616Pro Pathogenic ★★ same residue
ERCC2 p.Arg616Trp Pathogenic/Likely pathogenic ★★ same residue
ERCC2 p.Arg616Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
ERCC2 c.184-1_186del Likely pathogenic ★★ same condition
ERCC2 p.Ile456del Pathogenic/Likely pathogenic ★★ same condition
ERCC2 p.Ile619del Pathogenic ★★ same condition
ERCC2 p.Ser630fs Pathogenic/Likely pathogenic ★★ same condition
ERCC2 c.106-5_142del 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/ercc2-p-arg616fs (accessed [today's date]).

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