ERCC6L2 p.Ser415Phe
c.1244C>T · VCV4250552
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.48e-05%, nfe)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.454 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 6 | GERP 2.8, phastCons 1 |
| Regional constraint | o/e 0.86 | unconstrained · MANE · 92 kb · p 1.5e-06 · regional, not allelic |
| Overall | ||
| CADD | 23.4 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.48e-05%
European (non-Finnish) · 1/1,179,720 alleles
Overall
6.2e-05%
1/1,613,654 alleles · very rare
exomes 1/1,461,356 · genomes 0/152,298 · joint denominator
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
- ERCC6L2
- Protein
- p.Ser415Phe
- Coding
- c.1244C>T
- MANE Select
- NM_020207
- Type
- single nucleotide variant
- Location
- chr9:95921260 (GRCh38)
- Gene constraint
- LOEUF 0.792 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 58.11 · 2 PDB
Similar variants
- ERCC6L2 p.Ala26Val Uncertain significance ★★ same condition
- ERCC6L2 p.Ala290Val Uncertain significance ★★ same condition
- ERCC6L2 p.Ala345Thr Uncertain significance ★★ same condition
- ERCC6L2 p.Ala37Thr Uncertain significance ★★ same condition
- ERCC6L2 p.Ala460Thr Uncertain significance ★★ same condition
- ERCC6L2 p.Ala464Val Uncertain significance ★★ same condition
- ERCC6L2 p.Ala465Gly Uncertain significance ★★ same condition
- ERCC6L2 p.Ala546Ser 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/ercc6l2-p-ser415phe (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown