Is ERCC6 p.Ser797= (c.2391C>T) pathogenic?

ERCC6 p.Ser797= (c.2391C>T) is classified Conflicting classifications of pathogenicity in ERCC6 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-24). Rare (popmax 0.115%, mid); Associated with age related macular degeneration 5.

What condition is associated with ERCC6 p.Ser797= (c.2391C>T)?

ERCC6 p.Ser797= (c.2391C>T) is associated with age related macular degeneration 5, cerebrooculofacioskeletal syndrome 1, Cockayne syndrome type 2 (ClinVar).

How common is ERCC6 p.Ser797= (c.2391C>T) in the general population?

ERCC6 p.Ser797= (c.2391C>T) is rare (popmax 0.115%, mid) (gnomAD).

ERCC6 p.Ser797=

c.2391C>T · rs142641602 · VCV300066

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.115%, mid)

Conditions

age related macular degeneration 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.031	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2	GERP -0.53, phastCons 1
Overall
CADD	13.43	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.115% Middle Eastern · 7/6,084 alleles

Filtering AF 0.054% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0392%

Overall 0.0255% 411/1,613,498 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.699%	143
Middle Easterngrpmax	0.115%	869
Remaining individualsnot grpmax-eligible	0.0704%	1,420
Admixed American	0.06%	1,666
African / African-American	0.0107%	9,363
European (non-Finnish)	0.00848%	11,796
East Asian	0.00669%	14,959
South Asian	0.00549%	18,215
Finnishnot grpmax-eligible	0.00156%	63,976

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser797=
Coding: c.2391C>T
MANE Select: NM_000124
dbSNP: rs142641602
Type: single nucleotide variant
Location: chr10:49474234 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.12 · 12 PDB
Residue 797: an α-helix

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

Disease context

Also linked: cerebrooculofacioskeletal syndrome 1 Cockayne syndrome type 2

Similar variants

ERCC6 p.Ser797Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
ERCC6 p.Ala797= Likely benign ★ 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-ser797 (accessed [today's date]).

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