Is RTN2 p.Ser111Asn (c.332G>A) pathogenic?

RTN2 p.Ser111Asn (c.332G>A) is classified Uncertain significance in RTN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-23). AlphaMissense: likely benign (0.3191); No allele count reported in gnomAD v4.1 (AN 1,609,746).

How common is RTN2 p.Ser111Asn (c.332G>A) in the general population?

RTN2 p.Ser111Asn (c.332G>A) is no allele count reported in gnomAD v4.1 (AN 1,609,746) (gnomAD).

What do computational predictors say about RTN2 p.Ser111Asn (c.332G>A)?

AlphaMissense predicts likely benign (score 0.3191) — an in-silico prediction, not a clinical call.

RTN2 p.Ser111Asn

c.332G>A · VCV4527255

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3191 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,609,746)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3191	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -7.38	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 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 11 kb · p 0.23 · regional, not allelic
Overall
CADD	23.8	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

No allele count reported in gnomAD v4.1 (AN 1,609,746). 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: RTN2
Protein: p.Ser111Asn
Coding: c.332G>A
MANE Select: NM_005619
Type: single nucleotide variant
Location: chr19:45494753 (GRCh38)
Gene constraint: LOEUF 0.748 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.99
Residue 111: a UniProt-annotated variant site (in hmnr11; likely pathogenic); a UniProt-annotated variant site (in spg12; likely pathogenic); the 'disordered' region

Full RTN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RTN2 p.Glu50Ter Pathogenic/Likely pathogenic ★★ same type
RTN2 c.1497+3G>A Uncertain significance ★★ same type
RTN2 p.Ala529Thr Uncertain significance ★★ ⚠ same type
RTN2 p.Arg152Pro Uncertain significance ★★ ⚠ same type
RTN2 p.Arg252Trp Uncertain significance ★★ ⚠ same type
RTN2 p.Arg398Cys Uncertain significance ★★ ⚠ same type
RTN2 p.Arg406Trp Uncertain significance ★★ ⚠ same type
RTN2 p.Arg447Gln 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/rtn2-p-ser111asn (accessed [today's date]).

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