Is ERCC1 p.Pro202= (c.606C>T) pathogenic?

ERCC1 p.Pro202= (c.606C>T) is classified Likely benign in ERCC1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-01). Very rare (popmax 0.00238%, nfe).

How common is ERCC1 p.Pro202= (c.606C>T) in the general population?

ERCC1 p.Pro202= (c.606C>T) is very rare (popmax 0.00238%, nfe) (gnomAD).

ERCC1 p.Pro202=

c.606C>T · VCV3608988

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00238%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.71 · evaluated, not missing
Constraint at this position
Conservation	phyloP -7.4	GERP -3.2
Overall
CADD	0.093	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00238% European (non-Finnish) · 28/1,178,758 alleles

Filtering AF 0.00165% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00142%

Overall 0.00205% 33/1,612,408 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,590
European (non-Finnish)grpmax	0.00238%	42,099
East Asian	0.00223%	44,848
Finnishnot grpmax-eligible	0.00156%	63,916
African / African-American	0.00134%	74,852
South Asian	0.0011%	91,052

Ashkenazi Jewish 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: ERCC1
Protein: p.Pro202=
Coding: c.606C>T
MANE Select: NM_001983
Type: single nucleotide variant
Location: chr19:45414957 (GRCh38)
Gene constraint: LOEUF 1.306 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 77.48 · 14 PDB
Residue 202: an α-helix

Full ERCC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ERCC1 c.526-1G>A Likely pathogenic ★★ same type
ERCC1 p.Arg41Ter Pathogenic ★★ same type
ERCC1 c.843+52A>G Uncertain significance ★★ same type
ERCC1 p.Ala265Thr Uncertain significance ★★ ⚠ same type
ERCC1 p.Arg156Gln Uncertain significance ★★ ⚠ same type
ERCC1 p.Arg207Trp Uncertain significance ★★ ⚠ same type
ERCC1 p.Asn110Ser Uncertain significance ★★ ⚠ same type
ERCC1 p.Gly85Arg Uncertain significance ★★ ⚠ same type

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/ercc1-p-pro202 (accessed [today's date]).

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