Is ERCC6 p.Ala801= (c.2403C>T) pathogenic?

ERCC6 p.Ala801= (c.2403C>T) is classified Benign/Likely benign in ERCC6 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-14). Rare (popmax 0.8%, afr); Associated with age related macular degeneration 5.

What condition is associated with ERCC6 p.Ala801= (c.2403C>T)?

ERCC6 p.Ala801= (c.2403C>T) is associated with age related macular degeneration 5, cerebrooculofacioskeletal syndrome 1, Cockayne syndrome type 2 (ClinVar).

How common is ERCC6 p.Ala801= (c.2403C>T) in the general population?

ERCC6 p.Ala801= (c.2403C>T) is rare (popmax 0.8%, afr) (gnomAD).

ERCC6 p.Ala801=

c.2403C>T · rs114896216 · VCV194152

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.8%, afr)

Conditions

age related macular degeneration 5

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 0.39	GERP 0.062, phastCons 0.98
Overall
CADD	8.248	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.8% African / African-American · 600/74,990 alleles

Filtering AF 0.747% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.726%

Overall 0.0405% 654/1,613,970 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.8%	125
Remaining individualsnot grpmax-eligible	0.0496%	2,016
Middle Eastern	0.0495%	2,020
Admixed American	0.015%	6,669
South Asian	0.00329%	30,360
European (non-Finnish)	0.000678%	147,496

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.Ala801=
Coding: c.2403C>T
MANE Select: NM_000124
dbSNP: rs114896216
Type: single nucleotide variant
Location: chr10:49474222 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.12 · 12 PDB
Residue 801: 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.Ala801Val 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-ala801 (accessed [today's date]).

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