Is ERCC6 p.Val50= (c.150G>A) pathogenic?

ERCC6 p.Val50= (c.150G>A) is classified Conflicting classifications of pathogenicity in ERCC6 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-27). Rare (popmax 0.151%, nfe); Associated with cerebrooculofacioskeletal syndrome 1.

What condition is associated with ERCC6 p.Val50= (c.150G>A)?

ERCC6 p.Val50= (c.150G>A) is associated with cerebrooculofacioskeletal syndrome 1, age related macular degeneration 5, Cockayne syndrome type 2 (ClinVar).

How common is ERCC6 p.Val50= (c.150G>A) in the general population?

ERCC6 p.Val50= (c.150G>A) is rare (popmax 0.151%, nfe) (gnomAD).

ERCC6 p.Val50=

c.150G>A · rs80133923 · VCV190149

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.151%, nfe)

Conditions

cerebrooculofacioskeletal syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.69	acceptor gain · deltas
Pangolin	Δ0.56	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.2	GERP -3.8
Overall
CADD	16.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.151% European (non-Finnish) · 1,786/1,180,048 alleles

Filtering AF 0.145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.143%

Overall 0.119% 1,916/1,614,222 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.151%	661
Remaining individualsnot grpmax-eligible	0.109%	919
Admixed American	0.06%	1,667
Finnishnot grpmax-eligible	0.0187%	5,337
African / African-American	0.0173%	5,774
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606

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.Val50=
Coding: c.150G>A
MANE Select: NM_000124
dbSNP: rs80133923
Type: single nucleotide variant
Location: chr10:49532815 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.12 · 12 PDB
Residue 50: 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: age related macular degeneration 5 Cockayne syndrome type 2

Similar variants

ERCC6 p.Val50Met 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
ERCC6 c.2599-26A>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-val50 (accessed [today's date]).

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