ENG c.67+4G>A
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00135%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +4 | donor splice region (+4, within the first 6 intronic nt) · inside the BP7-excluded zone |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.33 | GERP -3.2, phastCons 0.99 |
| Non-coding constraint | Z 3.30 | 1 kb window · o/e 0.70 · regional · uncalibrated |
| Overall | ||
| CADD | 12.7 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00135%
African / African-American · 1/74,336 alleles
Overall
6.98e-05%
1/1,432,084 alleles · very rare
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.67+4G>A
- MANE Select
- NM_001114753
- dbSNP
- rs1309975584
- Type
- single nucleotide variant
- Location
- chr9:127854285 (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-67-plus-4g-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown