Is RTN2 p.Gln117= (c.351A>G) pathogenic?

RTN2 p.Gln117= (c.351A>G) is classified Benign/Likely benign in RTN2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-03-01). Rare (popmax 0.785%, nfe); Associated with hereditary spastic paraplegia.

What condition is associated with RTN2 p.Gln117= (c.351A>G)?

RTN2 p.Gln117= (c.351A>G) is associated with hereditary spastic paraplegia (ClinVar).

How common is RTN2 p.Gln117= (c.351A>G) in the general population?

RTN2 p.Gln117= (c.351A>G) is rare (popmax 0.785%, nfe) (gnomAD).

RTN2 p.Gln117=

c.351A>G · rs144028452 · VCV240193

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.785%, nfe)

Conditions

hereditary spastic paraplegia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.6	GERP -3.6
Overall
CADD	6.292	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.785% European (non-Finnish) · 9,263/1,179,950 alleles

Filtering AF 0.772% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.766%

Overall 0.636% 10,250/1,611,872 alleles · rare exomes 9,600/1,459,634 · genomes 650/152,238 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.785%	127
Finnishnot grpmax-eligible	0.747%	134
Remaining individualsnot grpmax-eligible	0.418%	239
Amishnot grpmax-eligible	0.22%	455
Ashkenazi Jewishnot grpmax-eligible	0.22%	455
Admixed American	0.163%	612
African / African-American	0.117%	853
Middle Eastern	0.033%	3,029
South Asian	0.00878%	11,385
East Asian	0.00223%	44,876

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: RTN2
Protein: p.Gln117=
Coding: c.351A>G
MANE Select: NM_005619
dbSNP: rs144028452
Type: single nucleotide variant
Location: chr19:45494734 (GRCh38)
Gene constraint: LOEUF 0.748 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.99
Residue 117: 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

Disease context

hereditary spastic paraplegia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RTN2 p.Arg85Cys Uncertain significance ★★ ⚠ same condition
RTN2 p.Tyr495Cys Uncertain significance ★★ ⚠ same condition
RTN2 p.Val404Met Uncertain significance ★★ ⚠ same condition
RTN2 p.Ala381= Benign/Likely benign ★★ same condition
RTN2 p.Ala531= Benign/Likely benign ★★ same condition
RTN2 p.Gly148= Benign/Likely benign ★★ same condition
RTN2 p.Gly390Ser Benign/Likely benign ★★ same condition
RTN2 p.Phe264Leu Benign/Likely benign ★★ ⚠ same condition

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-gln117 (accessed [today's date]).

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