Is RAPSN p.Arg397= (c.1189C>A) pathogenic?

RAPSN p.Arg397= (c.1189C>A) is classified Likely benign in RAPSN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-19). Very rare (popmax 0.000698%, nfe); Associated with congenital myasthenic syndrome 11.

What condition is associated with RAPSN p.Arg397= (c.1189C>A)?

RAPSN p.Arg397= (c.1189C>A) is associated with congenital myasthenic syndrome 11, fetal akinesia deformation sequence 1 (ClinVar).

How common is RAPSN p.Arg397= (c.1189C>A) in the general population?

RAPSN p.Arg397= (c.1189C>A) is very rare (popmax 0.000698%, nfe) (gnomAD).

RAPSN p.Arg397=

c.1189C>A · rs201796294 · VCV2927667

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000698%, nfe)

Conditions

congenital myasthenic syndrome 11

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.198	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP 1.5, phastCons 0.99
Overall
CADD	9.957	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000698% European (non-Finnish) · 8/1,146,908 alleles

Filtering AF 0.0003% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000217%

Overall 0.000516% 8/1,549,960 alleles · very rare exomes 8/1,397,710 · genomes 0/152,250 · 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: RAPSN
Protein: p.Arg397=
Coding: c.1189C>A
MANE Select: NM_005055
dbSNP: rs201796294
Type: single nucleotide variant
Location: chr11:47438025 (GRCh38)
Gene constraint: LOEUF 1.092 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.29

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

Disease context

congenital myasthenic syndrome 11 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: fetal akinesia deformation sequence 1

Similar variants

RAPSN p.Arg397Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
RAPSN p.Arg397Trp Likely benign ★ same residue
RAPSN c.1166+1G>T Pathogenic/Likely pathogenic ★★ same condition
RAPSN c.192+2T>G Pathogenic ★★ same condition
RAPSN c.531+1G>A Pathogenic/Likely pathogenic ★★ same condition
RAPSN c.531+1G>T Pathogenic/Likely pathogenic ★★ same condition
RAPSN c.913-1G>C Likely pathogenic ★★ same condition
RAPSN c.-199C>G Pathogenic/Likely pathogenic ★★ 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/rapsn-p-arg397 (accessed [today's date]).

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