ENOSF1 c.84+130A>C
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0646%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.053 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| Splice region | donor +130 | deep intronic (+130 nt into the intron) |
| SpliceAI | Δ0.27 | donor loss · deltas |
| Constraint at this position | ||
| Conservation | phyloP -0.99 | GERP -0.16, phastCons 0.001 |
| Non-coding constraint | Z -0.69 | 1 kb window · o/e 1.05 · regional · uncalibrated |
| Overall | ||
| CADD | 9.393 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0646%
East Asian · 26/40,220 alleles
Filtering AF
0.0453%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0388%
Overall
0.0053%
81/1,528,902 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0646% | 1,547 |
| African / African-American | 0.0501% | 1,996 |
| Admixed American | 0.0079% | 12,650 |
| Remaining individualsnot grpmax-eligible | 0.00672% | 14,885 |
| South Asian | 0.00479% | 20,861 |
| European (non-Finnish) | 0.000612% | 163,341 |
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
- ENOSF1
- Coding
- c.84+130A>C
- MANE Select
- NM_017512
- Type
- single nucleotide variant
- Location
- chr18:712374 (GRCh38)
- Gene constraint
- LOEUF 1.236 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 97.47 · 1 PDB
Similar variants
- ENOSF1 c.*1219T>C Benign ★★ same type
- TYMS c.556+1G>A Pathogenic ★ same type
- TYMS p.Arg271Ter Pathogenic ★ same type
- ENOSF1 c.84+108G>C Uncertain significance ★ same type
- ENOSF1 c.84+112A>C Uncertain significance ★ same type
- ENOSF1 c.84+114C>G Uncertain significance ★ same type
- ENOSF1 c.84+125T>C Uncertain significance ★ same type
- ENOSF1 c.84+130A>G 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/enosf1-c-84-plus-130a-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown