Is ERCC5 p.Arg372fs (c.1115_1118del) pathogenic?

ERCC5 p.Arg372fs (c.11151118del) is classified Pathogenic/Likely pathogenic in ERCC5 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-03-18). Very rare (popmax 0.00373%, nfe); Associated with cerebrooculofacioskeletal syndrome 3.

What condition is associated with ERCC5 p.Arg372fs (c.1115_1118del)?

ERCC5 p.Arg372fs (c.1115_1118del) is associated with cerebrooculofacioskeletal syndrome 3, xeroderma pigmentosum group G (ClinVar).

How common is ERCC5 p.Arg372fs (c.1115_1118del) in the general population?

ERCC5 p.Arg372fs (c.1115_1118del) is very rare (popmax 0.00373%, nfe) (gnomAD).

ERCC5 p.Arg372fs

c.1115_1118del · rs786200919 · VCV16574

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00373%, nfe)

Conditions

cerebrooculofacioskeletal syndrome 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.69	GERP -2.1
Overall
CADD	20.3	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00373% European (non-Finnish) · 44/1,180,044 alleles

Filtering AF 0.00283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00252%

Overall 0.00285% 46/1,614,048 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00373%	26,819
Remaining individualsnot grpmax-eligible	0.0016%	62,486
African / African-American	0.00133%	74,914

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: ERCC5
Protein: p.Arg372fs
Coding: c.1115_1118del
dbSNP: rs786200919
Type: Deletion
Location: chr13:102862263 (GRCh38)

Full ERCC5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cerebrooculofacioskeletal syndrome 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: xeroderma pigmentosum group G

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/ercc5-p-arg372fs (accessed [today's date]).

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