Is ERCC6 p.Glu43del (c.124GAG[1]) pathogenic?

ERCC6 p.Glu43del (c.124GAG[1]) is classified Uncertain significance in ERCC6 (ClinVar, Single submitter, 2 submitters; last evaluated 2026-01-27). Very rare (popmax 0.00549%, sas); Associated with cerebrooculofacioskeletal syndrome 1.

What condition is associated with ERCC6 p.Glu43del (c.124GAG[1])?

ERCC6 p.Glu43del (c.124GAG[1]) is associated with cerebrooculofacioskeletal syndrome 1, de Sanctis-Cacchione syndrome, Cockayne syndrome type 2 (ClinVar).

How common is ERCC6 p.Glu43del (c.124GAG[1]) in the general population?

ERCC6 p.Glu43del (c.124GAG[1]) is very rare (popmax 0.00549%, sas) (gnomAD).

ERCC6 p.Glu43del

c.124GAG[1] · rs751610688 · VCV556344

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Conditions

cerebrooculofacioskeletal syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.3	GERP -3.9

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00549% South Asian · 5/91,080 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.00041% 6/1,461,890 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,216
European (non-Finnish)	8.47e-05%	1,179,954

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: ERCC6
Protein: p.Glu43del
Coding: c.124GAG[1]
MANE Select: NM_000124
dbSNP: rs751610688
Type: Microsatellite
Location: chr10:49532836 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.12 · 12 PDB
Residue 43: the 'n-terminal domain; essential for its chromatin remodeling activity' region

Full ERCC6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cerebrooculofacioskeletal syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: de Sanctis-Cacchione syndrome Cockayne syndrome type 2

Similar variants

ERCC6 p.Asp366_Ser367insTer Pathogenic ★★ same condition
ERCC6 p.Cys573fs Pathogenic/Likely pathogenic ★★ same condition
ERCC6 p.Ser624fs Pathogenic ★★ same condition
ERCC6 p.Glu43Asp Uncertain significance ★★ ⚠ same residue
ERCC6 p.Lys1198fs Pathogenic ★ same condition
ERCC6 p.Thr587fs Likely pathogenic ★ same condition
ERCC6 p.Arg1039del Uncertain significance ★ same condition
ERCC6 p.Glu382_Glu384del Uncertain significance ★ 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/ercc6-p-glu43del (accessed [today's date]).

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