Is ERCC2 p.Arg156Ter (c.466C>T) pathogenic?

ERCC2 p.Arg156Ter (c.466C>T) is classified Pathogenic/Likely pathogenic in ERCC2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-02). Ultra-rare (popmax 0.0165%, mid); Associated with ERCC2-related disorder.

What condition is associated with ERCC2 p.Arg156Ter (c.466C>T)?

ERCC2 p.Arg156Ter (c.466C>T) is associated with ERCC2-related disorder, xeroderma pigmentosum group D, trichothiodystrophy 1, photosensitive (ClinVar).

How common is ERCC2 p.Arg156Ter (c.466C>T) in the general population?

ERCC2 p.Arg156Ter (c.466C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

ERCC2 p.Arg156Ter

c.466C>T · rs151235136 · VCV634432

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

ERCC2-related disorder

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 6 of 23
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.22	loss · gain 0.01 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 4.4	GERP 1.5, phastCons 1
Overall
CADD	41.0	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 0.0165% Middle Eastern · 1/6,060 alleles

Filtering AF 0.00378% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00345%

Overall 0.00465% 75/1,613,650 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,060
Remaining individualsnot grpmax-eligible	0.0096%	10,414
African / African-American	0.00533%	18,761
European (non-Finnish)	0.00483%	20,694
South Asian	0.00439%	22,764
Finnishnot grpmax-eligible	0.00312%	32,018
East Asian	0.00223%	44,884

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.Arg156Ter
Coding: c.466C>T
MANE Select: NM_000400
dbSNP: rs151235136
Type: single nucleotide variant
Location: chr19:45365053 (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 156: the helicase atp-binding domain; an α-helix

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

Disease context

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

Similar variants

ERCC2 p.Arg156= Benign/Likely benign ★★ same residue
ERCC2 p.Arg156Leu Uncertain significance ★ ⚠ same residue
MAG p.Glu156Asp 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

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-arg156ter (accessed [today's date]).

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