Is RTN2 p.Thr17= (c.51A>G) pathogenic?

RTN2 p.Thr17= (c.51A>G) is classified Benign in RTN2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-02). Common (popmax 9.58%, amr) — too common for a highly-penetrant pathogenic allele; Associated with Spastic paraplegia.

What condition is associated with RTN2 p.Thr17= (c.51A>G)?

RTN2 p.Thr17= (c.51A>G) is associated with Spastic paraplegia, hereditary spastic paraplegia (ClinVar).

RTN2 p.Thr17=

Q: How common is RTN2 p.Thr17= (c.51A>G) in the general population?

RTN2 p.Thr17= (c.51A>G) is common (popmax 9.58%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.51A>G · rs117156117 · VCV383326

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 9.58%, amr) — too common for a highly-penetrant pathogenic allele

Conditions

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 0.14	GERP -0.22, phastCons 0.97
Overall
CADD	10.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.58% Admixed American · 5,748/60,012 alleles

Filtering AF 9.37% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.29%

Overall 0.548% 8,844/1,614,148 alleles · common exomes 7,405/1,461,850 · genomes 1,439/152,298 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	9.58%	10
East Asian	4.51%	22
Remaining individualsnot grpmax-eligible	0.645%	155
South Asian	0.4%	250
Middle Eastern	0.215%	464
African / African-American	0.135%	743
European (non-Finnish)	0.0161%	6,211
Finnishnot grpmax-eligible	0.00156%	64,042

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.Thr17=
Coding: c.51A>G
MANE Select: NM_005619
dbSNP: rs117156117
Type: single nucleotide variant
Location: chr19:45495123 (GRCh38)
Gene constraint: LOEUF 0.748 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.99
Residue 17: the 'disordered' region

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

Disease context

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

Also linked: hereditary spastic paraplegia

Similar variants

RTN2 p.Thr17Ala Uncertain significance ★ ⚠ same residue
RTN2 p.Glu50Ter Pathogenic/Likely pathogenic ★★ same condition
RTN2 c.1497+3G>A Uncertain significance ★★ same condition
RTN2 p.Ala529Thr Uncertain significance ★★ ⚠ same condition
RTN2 p.Arg152Pro Uncertain significance ★★ ⚠ same condition
RTN2 p.Arg252Trp Uncertain significance ★★ ⚠ same condition
RTN2 p.Arg398Cys Uncertain significance ★★ ⚠ same condition
RTN2 p.Arg447Gln Uncertain significance ★★ ⚠ 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-thr17 (accessed [today's date]).

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