Is RAPSN p.Ser37= (c.111G>A) pathogenic?

RAPSN p.Ser37= (c.111G>A) is classified Likely benign in RAPSN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-02). Ultra-rare (popmax 0.02%, amr); Associated with congenital myasthenic syndrome 11.

What condition is associated with RAPSN p.Ser37= (c.111G>A)?

RAPSN p.Ser37= (c.111G>A) is associated with congenital myasthenic syndrome 11, congenital myasthenic syndrome, fetal akinesia deformation sequence 1 (ClinVar).

How common is RAPSN p.Ser37= (c.111G>A) in the general population?

RAPSN p.Ser37= (c.111G>A) is ultra-rare (popmax 0.02%, amr) (gnomAD).

RAPSN p.Ser37=

c.111G>A · rs146825957 · VCV767529

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, amr)

Conditions

congenital myasthenic syndrome 11

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 -12	GERP -4.6
Overall
CADD	3.143	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.02% Admixed American · 12/60,034 alleles

Filtering AF 0.0115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00898%

Overall 0.00204% 33/1,614,154 alleles · ultra-rare exomes 30/1,461,824 · genomes 3/152,330 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.02%	5,003
Ashkenazi Jewishnot grpmax-eligible	0.00675%	14,804
East Asian	0.00446%	22,432
African / African-American	0.004%	25,020
Remaining individualsnot grpmax-eligible	0.0032%	31,256
South Asian	0.0022%	45,544
European (non-Finnish)	0.000847%	118,005

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.Ser37=
Coding: c.111G>A
MANE Select: NM_005055
dbSNP: rs146825957
Type: single nucleotide variant
Location: chr11:47448854 (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: congenital myasthenic syndrome fetal akinesia deformation sequence 1

Similar variants

RAPSN p.Ser37Leu Uncertain significance ★ ⚠ 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
RAPSN c.-210A>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-ser37 (accessed [today's date]).

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