Is RTN3 p.Ser288Leu (c.863C>T) pathogenic?

RTN3 p.Ser288Leu (c.863C>T) is classified Likely benign in RTN3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-14). AlphaMissense: likely benign (0.0654); Very rare (popmax 8.47e-05%, nfe).

How common is RTN3 p.Ser288Leu (c.863C>T) in the general population?

RTN3 p.Ser288Leu (c.863C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about RTN3 p.Ser288Leu (c.863C>T)?

AlphaMissense predicts likely benign (score 0.0654) — an in-silico prediction, not a clinical call.

RTN3 p.Ser288Leu

c.863C>T · rs2011589268 · VCV2612194

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0654 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0654	likely benign
REVEL	0.017	moderately benign-leaning
SaProt	LLR -6.64	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 1.4	GERP -3.7, phastCons 0.008
Regional constraint	o/e 1.07	unconstrained · MANE · 68 kb · p 0.037 · regional, not allelic
Overall
CADD	11.73	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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,044 alleles

Overall 6.2e-05% 1/1,614,066 alleles · very rare exomes 0/1,461,882 · genomes 1/152,184 · joint denominator

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: RTN3
Protein: p.Ser288Leu
Coding: c.863C>T
MANE Select: NM_001265589
dbSNP: rs2011589268
Type: single nucleotide variant
Location: chr11:63719365 (GRCh38)
Gene constraint: LOEUF 0.712 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 43.42 · 1 PDB

Full RTN3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RTN3 p.Ser10= Benign ★★ same type
RTN3 p.Ala198Thr Uncertain significance ★ ⚠ same type
RTN3 p.Ala256Thr Uncertain significance ★ ⚠ same type
RTN3 p.Ala2Val Uncertain significance ★ ⚠ same type
RTN3 p.Ala321Val Uncertain significance ★ ⚠ same type
RTN3 p.Ala448Gly Uncertain significance ★ ⚠ same type
RTN3 p.Ala510Pro Uncertain significance ★ ⚠ same type
RTN3 p.Ala657Val Uncertain significance ★ ⚠ 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/rtn3-p-ser288leu (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown