Is ERCC2 p.Asp711= (c.2133C>T) pathogenic?

ERCC2 p.Asp711= (c.2133C>T) is classified Benign/Likely benign in ERCC2 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). Common (popmax 35.6%, mid) — too common for a highly-penetrant pathogenic allele; Associated with trichothiodystrophy 1, photosensitive.

What condition is associated with ERCC2 p.Asp711= (c.2133C>T)?

ERCC2 p.Asp711= (c.2133C>T) is associated with trichothiodystrophy 1, photosensitive, xeroderma pigmentosum group D, cerebrooculofacioskeletal syndrome 2 (ClinVar).

ERCC2 p.Asp711=

Q: How common is ERCC2 p.Asp711= (c.2133C>T) in the general population?

ERCC2 p.Asp711= (c.2133C>T) is common (popmax 35.6%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2133C>T · rs1052555 · VCV256018

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 35.6%, mid) — too common for a highly-penetrant pathogenic allele

Conditions

trichothiodystrophy 1, photosensitive

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 -6.5	GERP -3.1
Overall
CADD	0.335	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 35.6% Middle Eastern · 2,151/6,050 alleles

Filtering AF 34.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 33.8%

Overall 30.6% 494,239/1,613,738 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	41.8%	2
Finnishnot grpmax-eligible	39.1%	3
Ashkenazi Jewishnot grpmax-eligible	37.3%	3
Middle Easterngrpmax	35.6%	3
South Asian	33.6%	3
European (non-Finnish)	32.7%	3
Remaining individualsnot grpmax-eligible	29.7%	3
Admixed American	17.2%	6
African / African-American	10.7%	9
East Asian	4.53%	22

Amish 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: ERCC2
Protein: p.Asp711=
Coding: c.2133C>T
MANE Select: NM_000400
dbSNP: rs1052555
Type: single nucleotide variant
Location: chr19:45352266 (GRCh38)
Gene constraint: LOEUF 1.089 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.74 · 55 PDB
Residue 711: an α-helix

Full ERCC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Also linked: xeroderma pigmentosum group D cerebrooculofacioskeletal syndrome 2

Similar variants

ERCC2 p.Asp711Asn Uncertain significance ★ ⚠ same residue
ERCC2 p.Asp711Val Uncertain significance ★ ⚠ same residue
ERCC2 c.1238-1G>C Likely pathogenic ★★ same condition
ERCC2 c.1308-2A>G Likely pathogenic ★★ same condition
ERCC2 c.1378-1G>T Pathogenic/Likely pathogenic ★★ same condition
ERCC2 c.1479+2T>C Pathogenic/Likely pathogenic ★★ same condition
ERCC2 c.1480-1G>C Pathogenic/Likely pathogenic ★★ same condition
ERCC2 c.1480-2A>C 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/ercc2-p-asp711 (accessed [today's date]).

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