ENG p.Val568fs
c.1701del · rs1564452060 · VCV618625
ClinGen expert panel — Hereditary Hemorrhagic Telangiectasia VCEP
Pathogenic for telangiectasia, hereditary hemorrhagic, type 1. Applied ACMG criteria (verbatim):
PVS1 PM2_Supporting PS4_Supporting
Curation rationale (ClinGen, verbatim)
The NM_001114753.3: c.1701del (p.Val568Serfs*5) variant in ENG is a frameshift variant predicted to cause a premature stop codon in biologically relevant exon 13 (out of 15) leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). This variant has been reported in a proband with a phenotype consistent of HHT (PS4_Supporting; Internal lab contributors). In summary, this variant meets the criteria to be classified as pathogenic for autosomal dominant hereditary hemorrhagic telangiectasia based on the ACMG/AMP criteria applied, as specified by the ClinGen Hereditary Hemorrhagic Telangiectasia Variant Curation Expert Panel: PVS1, PM2_Supporting, PS4_Supporting (specification version 1.0.0; 1/4/2024).
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 13 of 15 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP -0.033 | GERP -0.7, phastCons 0.001 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
No gnomAD frequency available for this variant. 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
- Protein
- p.Val568fs
- Coding
- c.1701del
- MANE Select
- NM_001114753
- dbSNP
- rs1564452060
- Type
- Deletion
- Location
- chr9:127817189 (GRCh38)
- Gene constraint
- LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 80.84 · 3 PDB
- Residue 568
- a β-strand
Disease context
telangiectasia, hereditary hemorrhagic, type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Hereditary hemorrhagic telangiectasia (Orphanet):
- Inheritance
- Autosomal dominant
- Onset
- All ages
- Prevalence
- 1-5 / 10 000 (Europe)
Similar variants
- ENG p.Val568Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
- ENG p.Ala312fs Pathogenic ★★ same condition
- ENG p.Ala55fs Pathogenic ★★ same condition
- ENG p.Arg232_Thr233del Likely pathogenic ★★ same condition
- ENG p.Arg399fs Pathogenic/Likely pathogenic ★★ same condition
- ENG p.Asp246fs Pathogenic ★★ same condition
- ENG p.Cys493fs Pathogenic ★★ same condition
- ENG p.Glu38fs 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-p-val568fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown