Is ERCC3 p.Gln711Ter (c.2131C>T) pathogenic?

ERCC3 p.Gln711Ter (c.2131C>T) is classified Pathogenic/Likely pathogenic in ERCC3 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-20). Very rare (popmax 0.00833%, amr); Associated with Inborn genetic diseases.

What condition is associated with ERCC3 p.Gln711Ter (c.2131C>T)?

ERCC3 p.Gln711Ter (c.2131C>T) is associated with Inborn genetic diseases, xeroderma pigmentosum group B, trichothiodystrophy 2, photosensitive (ClinVar).

How common is ERCC3 p.Gln711Ter (c.2131C>T) in the general population?

ERCC3 p.Gln711Ter (c.2131C>T) is very rare (popmax 0.00833%, amr) (gnomAD).

ERCC3 p.Gln711Ter

c.2131C>T · rs763315862 · VCV1458593

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 14 of 15
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Overall
CADD	46.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00833% Admixed American · 5/60,002 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.00062% 10/1,614,052 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	12,000
Remaining individualsnot grpmax-eligible	0.0032%	31,245
European (non-Finnish)	0.000254%	393,340

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: ERCC3
Protein: p.Gln711Ter
Coding: c.2131C>T
MANE Select: NM_000122
dbSNP: rs763315862
Type: single nucleotide variant
Location: chr2:127259382 (GRCh38)
Gene constraint: LOEUF 0.797 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.34 · 56 PDB
Residue 711: an α-helix

Full ERCC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: xeroderma pigmentosum group B trichothiodystrophy 2, photosensitive

Similar variants

ERCC3 c.1828-1G>C Likely pathogenic ★★ same condition
ERCC3 c.471+1G>A Pathogenic ★★ same condition
ERCC3 c.657+1G>A Likely pathogenic ★★ same condition
ERCC3 p.Arg109Ter Pathogenic/Likely pathogenic ★★ same condition
ERCC3 p.Arg195Ter Pathogenic ★★ same condition
ERCC3 p.Arg425Ter Pathogenic ★★ same condition
ERCC3 p.Arg452Ter Pathogenic/Likely pathogenic ★★ same condition
ERCC3 p.Arg530Ter 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/ercc3-p-gln711ter (accessed [today's date]).

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