Is ERCC2 p.Ala356= (c.1068C>T) pathogenic?

ERCC2 p.Ala356= (c.1068C>T) is classified Likely benign in ERCC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-12). Very rare (popmax 0.00119%, sas); Associated with Inborn genetic diseases.

What condition is associated with ERCC2 p.Ala356= (c.1068C>T)?

ERCC2 p.Ala356= (c.1068C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ERCC2 p.Ala356= (c.1068C>T) in the general population?

ERCC2 p.Ala356= (c.1068C>T) is very rare (popmax 0.00119%, sas) (gnomAD).

ERCC2 p.Ala356=

c.1068C>T · rs1185861657 · VCV1782485

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00119%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.6	GERP 0.73, phastCons 1
Overall
CADD	10.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00119% South Asian · 1/84,302 alleles

Overall 0.00013% 2/1,539,050 alleles · very rare exomes 1/1,386,794 · genomes 1/152,256 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00119%	84,302
European (non-Finnish)	8.71e-05%	1,148,755

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.Ala356=
Coding: c.1068C>T
MANE Select: NM_000400
dbSNP: rs1185861657
Type: single nucleotide variant
Location: chr19:45363793 (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 356: an α-helix

Full ERCC2 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

ERCC2 p.Ala356Pro Uncertain significance ★ ⚠ same residue
ERCC2 p.Ala356Thr Uncertain significance ★ ⚠ same residue
ERCC2 p.Ala356Val Uncertain significance ★ ⚠ same residue
ERCC2 p.Ala725Pro Pathogenic/Likely pathogenic ★★ same condition
ERCC2 p.Arg616Pro Pathogenic ★★ same condition
ERCC2 p.Ala108Thr Uncertain significance ★★ ⚠ same condition
ERCC2 p.Ala144Val Uncertain significance ★★ ⚠ same condition
ERCC2 p.Ala226Thr 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/ercc2-p-ala356 (accessed [today's date]).

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