Is RTN2 p.Ser19Phe (c.56C>T) pathogenic?

RTN2 p.Ser19Phe (c.56C>T) is classified Uncertain significance in RTN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-13). AlphaMissense: likely pathogenic (0.7358); Very rare (popmax 0.000424%, nfe); Associated with Inborn genetic diseases.

What condition is associated with RTN2 p.Ser19Phe (c.56C>T)?

RTN2 p.Ser19Phe (c.56C>T) is associated with Inborn genetic diseases (ClinVar).

How common is RTN2 p.Ser19Phe (c.56C>T) in the general population?

RTN2 p.Ser19Phe (c.56C>T) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about RTN2 p.Ser19Phe (c.56C>T)?

AlphaMissense predicts likely pathogenic (score 0.7358) — an in-silico prediction, not a clinical call.

RTN2 p.Ser19Phe

c.56C>T · rs2513744343 · VCV2334573

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7358 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7358	likely pathogenic
REVEL	0.141	moderately benign-leaning
SaProt	LLR -8.99	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 11 kb · p 0.23 · regional, not allelic
Overall
CADD	28.1	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 0.000424% European (non-Finnish) · 5/1,180,034 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,614,170 alleles · very rare exomes 5/1,461,862 · genomes 0/152,308 · 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: RTN2
Protein: p.Ser19Phe
Coding: c.56C>T
MANE Select: NM_005619
dbSNP: rs2513744343
Type: single nucleotide variant
Location: chr19:45495118 (GRCh38)
Gene constraint: LOEUF 0.748 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.99
Residue 19: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RTN2 p.Arg406Trp Uncertain significance ★★ ⚠ same condition
RTN2 p.Arg496Gln Uncertain significance ★★ ⚠ same condition
RTN2 p.Arg91His Uncertain significance ★★ ⚠ same condition
RTN2 p.Asn177Ser Uncertain significance ★★ ⚠ same condition
RTN2 p.Asp418Glu Uncertain significance ★★ same condition
RTN2 p.Gln512Arg Uncertain significance ★★ ⚠ same condition
RTN2 p.Glu169Lys Uncertain significance ★★ ⚠ same condition
RTN2 p.Glu249Lys 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-ser19phe (accessed [today's date]).

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