Is ERCC6 p.Phe779= (c.2337C>T) pathogenic?

ERCC6 p.Phe779= (c.2337C>T) is classified Conflicting classifications of pathogenicity in ERCC6 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-28). Ultra-rare (popmax 0.0267%, eas); Associated with cerebrooculofacioskeletal syndrome 1.

What condition is associated with ERCC6 p.Phe779= (c.2337C>T)?

ERCC6 p.Phe779= (c.2337C>T) is associated with cerebrooculofacioskeletal syndrome 1, age related macular degeneration 5, Cockayne syndrome type 2 (ClinVar).

How common is ERCC6 p.Phe779= (c.2337C>T) in the general population?

ERCC6 p.Phe779= (c.2337C>T) is ultra-rare (popmax 0.0267%, eas) (gnomAD).

ERCC6 p.Phe779=

c.2337C>T · rs114490473 · VCV300069

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, eas)

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP -0.32, phastCons 1
Overall
CADD	11.49	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0267% East Asian · 12/44,870 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.0107% 172/1,613,600 alleles · ultra-rare exomes 162/1,461,734 · genomes 10/151,866 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0267%	3,739
Remaining individualsnot grpmax-eligible	0.0128%	7,809
European (non-Finnish)	0.012%	8,309
South Asian	0.011%	9,106

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.Phe779=
Coding: c.2337C>T
MANE Select: NM_000124
dbSNP: rs114490473
Type: single nucleotide variant
Location: chr10:49476260 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.12 · 12 PDB
Residue 779: an α-helix

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: age related macular degeneration 5 Cockayne syndrome type 2

Similar variants

ERCC6 p.Phe779fs Likely pathogenic ★ same residue
ERCC6 p.Phe779Val Uncertain significance ★ ⚠ same residue
ERCC6 c.1397+1G>C Likely pathogenic ★★ same condition
ERCC6 c.1526+1G>T Pathogenic/Likely pathogenic ★★ same condition
ERCC6 c.2169+1G>A Likely pathogenic ★★ same condition
ERCC6 c.2170-1G>A Pathogenic/Likely pathogenic ★★ same condition
ERCC6 c.2286+1G>A Pathogenic/Likely pathogenic ★★ same condition
ERCC6 c.2287-2A>G Pathogenic/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/ercc6-p-phe779 (accessed [today's date]).

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