Is ERCC6 p.Pro1032Arg (c.3095C>G) pathogenic?

ERCC6 p.Pro1032Arg (c.3095C>G) is classified Conflicting classifications of pathogenicity in ERCC6 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-05). AlphaMissense: likely benign (0.086); Ultra-rare (popmax 0.0318%, sas); Associated with Inborn genetic diseases.

What condition is associated with ERCC6 p.Pro1032Arg (c.3095C>G)?

ERCC6 p.Pro1032Arg (c.3095C>G) is associated with Inborn genetic diseases (ClinVar).

How common is ERCC6 p.Pro1032Arg (c.3095C>G) in the general population?

ERCC6 p.Pro1032Arg (c.3095C>G) is ultra-rare (popmax 0.0318%, sas) (gnomAD).

What do computational predictors say about ERCC6 p.Pro1032Arg (c.3095C>G)?

AlphaMissense predicts likely benign (score 0.086) — an in-silico prediction, not a clinical call.

ERCC6 p.Pro1032Arg

c.3095C>G · rs775549101 · VCV2689031

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.086 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0318%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.086	likely benign
REVEL	0.467	indeterminate
SaProt	LLR -6.44	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 74 kb · p 0.017 · regional, not allelic
Overall
CADD	21.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0318% South Asian · 29/91,066 alleles

Filtering AF 0.0228% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0196%

Overall 0.00205% 30/1,461,612 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0318%	3,140
Remaining individualsnot grpmax-eligible	0.0016%	62,502

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: ERCC6
Protein: p.Pro1032Arg
Coding: c.3095C>G
MANE Select: NM_000124
dbSNP: rs775549101
Type: single nucleotide variant
Location: chr10:49470865 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.12 · 12 PDB

Full ERCC6 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

Similar variants

ERCC6 c.1397+1G>C Likely pathogenic ★★ same condition
ERCC6 p.Arg176Ter Pathogenic ★★ same condition
ERCC6 p.Arg612Ter Pathogenic/Likely pathogenic ★★ same condition
ERCC6 p.Arg857Ter Pathogenic ★★ same condition
ERCC6 p.Gln723Ter Pathogenic/Likely pathogenic ★★ same condition
ERCC6 p.Ser687Leu Pathogenic ★★ same condition
ERCC6 p.Ala1075Thr Uncertain significance ★★ ⚠ same condition
ERCC6 p.Ala1167Asp Uncertain significance ★★ ⚠ 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/ercc6-p-pro1032arg (accessed [today's date]).

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