Is RAPSN p.Cys366= (c.1098C>T) pathogenic?

RAPSN p.Cys366= (c.1098C>T) is classified Likely benign in RAPSN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-10). Rare (popmax 0.152%, sas); Associated with fetal akinesia deformation sequence 1.

What condition is associated with RAPSN p.Cys366= (c.1098C>T)?

RAPSN p.Cys366= (c.1098C>T) is associated with fetal akinesia deformation sequence 1, congenital myasthenic syndrome 11 (ClinVar).

How common is RAPSN p.Cys366= (c.1098C>T) in the general population?

RAPSN p.Cys366= (c.1098C>T) is rare (popmax 0.152%, sas) (gnomAD).

RAPSN p.Cys366=

c.1098C>T · rs139525851 · VCV259624

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.152%, sas)

Conditions

fetal akinesia deformation sequence 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.466	indeterminate
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -2.4	GERP -4.5
Overall
CADD	6.137	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.152% South Asian · 130/85,572 alleles

Filtering AF 0.131% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.123%

Overall 0.0167% 263/1,570,356 alleles · rare exomes 247/1,418,130 · genomes 16/152,226 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.152%	658
African / African-American	0.0323%	3,097
European (non-Finnish)	0.00891%	11,220
Remaining individualsnot grpmax-eligible	0.00659%	15,173
East Asian	0.00233%	43,000
Admixed American	0.00184%	54,394

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.Cys366=
Coding: c.1098C>T
MANE Select: NM_005055
dbSNP: rs139525851
Type: single nucleotide variant
Location: chr11:47438800 (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

fetal akinesia deformation sequence 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: congenital myasthenic syndrome 11

Similar variants

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
RAPSN c.-210A>G Pathogenic/Likely pathogenic ★★ same condition
RAPSN p.Ala142Asp 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-cys366 (accessed [today's date]).

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