ENG p.Gln174Pro
c.521A>C · VCV4690057
Computational evidence
| Protein change | ||
| AlphaMissense | 0.0745 | likely benign |
|---|---|---|
| REVEL | 0.076 | moderately benign-leaning |
| SaProt | LLR -8.98 | tolerated |
| ⇒ AlphaMissense, REVEL and SaProt all call this tolerated. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 2.5 | GERP -0.12, phastCons 1 |
| Regional constraint | o/e 0.86 | unconstrained · MANE · 39 kb · p 5.2e-05 · regional, not allelic |
| Overall | ||
| CADD | 16.88 | PHRED · no single calibrated threshold — expert panels disagree |
ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- ENG
- Protein
- p.Gln174Pro
- Coding
- c.521A>C
- MANE Select
- NM_001114753
- Type
- single nucleotide variant
- Location
- chr9:127826512 (GRCh38)
- Gene constraint
- LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 80.84 · 3 PDB
- Residue 174
- a disulfide bond; the 'required for interaction with gdf2' region; the 'or2' region
Similar variants
- ENG p.Gln174Ter Pathogenic ★ same residue
- ENG p.Gln174Arg Uncertain significance ★ same residue
- ENG p.Gln174fs Likely pathogenic ★ same residue
- 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
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-gln174pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown