RTN4 p.Ser696Pro
c.2086T>C · VCV3791349
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.5363 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
0/2 damaging
REVEL, SaProt · AlphaMissense indeterminate
Computational evidence
| Protein change | ||
| AlphaMissense | 0.5363 | ambiguous |
|---|---|---|
| REVEL | 0.283 | benign-leaning |
| SaProt | LLR -6.19 | tolerated |
| ⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 1.7, phastCons 1 |
| Regional constraint | o/e 1.19 | unconstrained · MANE · 77 kb · p 3e-13 · regional, not allelic |
| Overall | ||
| CADD | 25.5 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
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
- RTN4
- Protein
- p.Ser696Pro
- Coding
- c.2086T>C
- MANE Select
- NM_020532
- Type
- single nucleotide variant
- Location
- chr2:55026013 (GRCh38)
- Gene constraint
- LOEUF 0.546 · pLI 0.38 (gnomAD)
- Structure
- AlphaFold pLDDT 40.92 · 2 PDB
Similar variants
- RTN4 p.Glu899Gln Benign ★★ same type
- RTN4 p.Gly1070Ala Likely benign ★★ same type
- RTN4 p.Leu620= Benign ★★ same type
- RTN4 p.Leu814Met Likely benign ★★ same type
- RTN4 p.Pro992= Benign ★★ same type
- RTN4 p.Ser440Asn Benign ★★ same type
- RTN4 p.Ser920Cys Benign ★★ same type
- RTN4 p.Thr450Met Benign ★★ 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/rtn4-p-ser696pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown