ERCC6L2 p.Pro1306=
c.3918A>G · rs757319250 · VCV1622434
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0685%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.014 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 3.3 | GERP 0.27, phastCons 0.03 |
| Overall | ||
| CADD | 3.289 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0685%
Admixed American · 36/52,540 alleles
Filtering AF
0.0509%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0448%
Overall
0.00512%
70/1,367,258 alleles · ultra-rare
exomes 63/1,215,038 · genomes 7/152,220 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0685% | 1,459 |
| Remaining individualsnot grpmax-eligible | 0.0152% | 6,584 |
| African / African-American | 0.0118% | 8,466 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00983% | 10,176 |
| South Asian | 0.00341% | 29,310 |
| European (non-Finnish) | 0.00137% | 72,985 |
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.Pro1306=
- Coding
- c.3918A>G
- MANE Select
- NM_020207
- dbSNP
- rs757319250
- Type
- single nucleotide variant
- Location
- chr9:96012468 (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 c.950+2T>G Likely pathogenic ★★ same type
- ERCC6L2 p.Arg1255Ter Pathogenic/Likely pathogenic ★★ same type
- ERCC6L2 p.Arg644Ter Pathogenic ★★ same type
- ERCC6L2 p.Arg663Ter Pathogenic ★★ same type
- ERCC6L2 p.Gln7Ter Pathogenic/Likely pathogenic ★★ same type
- ERCC6L2 p.Gly301Ter Pathogenic/Likely pathogenic ★★ same type
- ERCC6L2 p.Ala1510Thr Uncertain significance ★★ same type
- ERCC6L2 p.Ala26Val 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/ercc6l2-p-pro1306 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown