Is ERCC2 p.Tyr544= (c.1632C>T) pathogenic?

ERCC2 p.Tyr544= (c.1632C>T) is classified Benign/Likely benign in ERCC2 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-27). Rare (popmax 0.482%, afr); Associated with xeroderma pigmentosum group D.

What condition is associated with ERCC2 p.Tyr544= (c.1632C>T)?

ERCC2 p.Tyr544= (c.1632C>T) is associated with xeroderma pigmentosum group D, trichothiodystrophy 1, photosensitive, cerebrooculofacioskeletal syndrome 2 (ClinVar).

How common is ERCC2 p.Tyr544= (c.1632C>T) in the general population?

ERCC2 p.Tyr544= (c.1632C>T) is rare (popmax 0.482%, afr) (gnomAD).

ERCC2 p.Tyr544=

Q: How is Xeroderma pigmentosum-Cockayne syndrome complex inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1632C>T · rs147605089 · VCV712863

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.482%, afr)

Conditions

xeroderma pigmentosum group D

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 7.4	GERP 1.5, phastCons 1
Overall
CADD	8.843	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.482% African / African-American · 362/75,040 alleles

Filtering AF 0.441% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.425%

Overall 0.0252% 407/1,614,104 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.482%	207
Remaining individualsnot grpmax-eligible	0.0288%	3,472
Admixed American	0.0283%	3,531
Middle Eastern	0.0165%	6,062
South Asian	0.0011%	91,086
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: ERCC2
Protein: p.Tyr544=
Coding: c.1632C>T
MANE Select: NM_000400
dbSNP: rs147605089
Type: single nucleotide variant
Location: chr19:45354763 (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 544: an α-helix; the 'mediates interaction with mms19' region

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

Disease context

xeroderma pigmentosum group D — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: trichothiodystrophy 1, photosensitive cerebrooculofacioskeletal syndrome 2 xeroderma pigmentosum

For Xeroderma pigmentosum-Cockayne syndrome complex (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

MAG p.Glu544= Likely benign ★ 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
ERCC2 c.1544-1G>T 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-tyr544 (accessed [today's date]).

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