Is RTN3 p.Arg795Cys (c.2383C>T) pathogenic?

RTN3 p.Arg795Cys (c.2383C>T) is classified Uncertain significance in RTN3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-09). AlphaMissense: likely benign (0.0787); Ultra-rare (popmax 0.0825%, mid).

How common is RTN3 p.Arg795Cys (c.2383C>T) in the general population?

RTN3 p.Arg795Cys (c.2383C>T) is ultra-rare (popmax 0.0825%, mid) (gnomAD).

What do computational predictors say about RTN3 p.Arg795Cys (c.2383C>T)?

AlphaMissense predicts likely benign (score 0.0787) — an in-silico prediction, not a clinical call.

RTN3 p.Arg795Cys

c.2383C>T · rs201862583 · VCV3157020

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0787 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0825%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0787	likely benign
REVEL	0.092	moderately benign-leaning
SaProt	LLR -8.23	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.83	GERP 0.6, phastCons 0.2
Regional constraint	o/e 1.07	unconstrained · MANE · 68 kb · p 0.037 · regional, not allelic
Overall
CADD	18.58	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

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0825% Middle Eastern · 5/6,062 alleles

Filtering AF 0.0527% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0513%

Overall 0.0469% 757/1,614,032 alleles · ultra-rare exomes 703/1,461,738 · genomes 54/152,294 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0825%	1,212
Admixed American	0.06%	1,667
European (non-Finnish)	0.0563%	1,777
Remaining individualsnot grpmax-eligible	0.0448%	2,233
African / African-American	0.0147%	6,822
South Asian	0.0121%	8,280
East Asian	0.00223%	44,886
Finnishnot grpmax-eligible	0.00156%	63,934

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.Arg795Cys
Coding: c.2383C>T
MANE Select: NM_001265589
dbSNP: rs201862583
Type: single nucleotide variant
Location: chr11:63720885 (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.Arg795Ser Uncertain significance ★ ⚠ same residue
RTN3 p.Arg795His Likely benign ★ same residue
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

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-arg795cys (accessed [today's date]).

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