ENG c.991+58A>T
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 6.24%, afr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +58 | deep intronic (+58 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -6.4 | GERP -1.9 |
| Overall | ||
| CADD | 0.011 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
6.24%
African / African-American · 4,154/66,530 alleles
Filtering AF
6.09%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 6.02%
Overall
0.35%
4,957/1,417,610 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 6.24% | 16 |
| Middle Eastern | 0.626% | 160 |
| Admixed American | 0.569% | 176 |
| Ashkenazi Jewishnot grpmax-eligible | 0.48% | 208 |
| Remaining individualsnot grpmax-eligible | 0.469% | 213 |
| European (non-Finnish) | 0.0191% | 5,224 |
| South Asian | 0.0131% | 7,627 |
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
- ENG
- Coding
- c.991+58A>T
- MANE Select
- NM_001114753
- dbSNP
- rs12002508
- Type
- single nucleotide variant
- Location
- chr9:127824742 (GRCh38)
- Gene constraint
- LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 80.84 · 3 PDB
Similar variants
- ENG p.Arg529His Pathogenic ★★★ ⚠ same type
- ENG p.Asn423Ser Likely pathogenic ★★★ ⚠ same type
- ENG p.Cys382Tyr Pathogenic ★★★ same type
- ENG p.Cys549Gly Likely pathogenic ★★★ same type
- ENG p.Gly331Ser Pathogenic ★★★ ⚠ same type
- ENG p.Gly603Arg Likely pathogenic ★★★ same type
- ENG p.Leu221Pro Likely pathogenic ★★★ same type
- ENG p.Leu506His Likely pathogenic ★★★ 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/eng-c-991-plus-58a-t (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown