ENG c.67+2T>C
Pathogenic/Likely pathogenic
Multiple submitters
Classification
Pathogenic/Likely pathogenic
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
Consequence
canonical splice-site (±1/±2)
predicted LoF
gnomAD v4.1
Not reported
no allele count reported in gnomAD v4.1 (AN 1,585,192)
Conditions
2
Cardiovascular phenotype
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Consequence | canonical splice-site (±1/±2) | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| Splicing | ||
| Splice region | donor +2 | canonical splice dinucleotide (donor +2) · inside the BP7-excluded zone |
| SpliceAI | Δ0.93 | donor loss · deltas |
| Pangolin | Δ0.72 | loss · gain 0.16 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 2.6, phastCons 1 |
| Non-coding constraint | Z 3.30 | 1 kb window · o/e 0.70 · regional · uncalibrated |
| Overall | ||
| CADD | 33.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
No allele count reported in gnomAD v4.1 (AN 1,585,192). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.
Variant & gene context
- Gene
- ENG
- Coding
- c.67+2T>C
- MANE Select
- NM_001114753
- dbSNP
- rs2131936480
- Type
- single nucleotide variant
- Location
- chr9:127854287 (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 condition
- ENG p.Asn423Ser Likely pathogenic ★★★ ⚠ same condition
- ENG p.Cys382Tyr Pathogenic ★★★ same condition
- ENG p.Cys549Gly Likely pathogenic ★★★ same condition
- ENG p.Gly331Ser Pathogenic ★★★ ⚠ same condition
- ENG p.Gly603Arg Likely pathogenic ★★★ same condition
- ENG p.Leu221Pro Likely pathogenic ★★★ same condition
- ENG p.Leu506His Likely pathogenic ★★★ 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/eng-c-67-plus-2t-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown