Is RAPSN p.Phe65= (c.195C>T) pathogenic?

RAPSN p.Phe65= (c.195C>T) is classified Likely benign in RAPSN (ClinVar, Single submitter, 2 submitters; last evaluated 2024-09-05). Ultra-rare (popmax 0.0164%, mid); Associated with congenital myasthenic syndrome 11.

What condition is associated with RAPSN p.Phe65= (c.195C>T)?

RAPSN p.Phe65= (c.195C>T) is associated with congenital myasthenic syndrome 11, fetal akinesia deformation sequence 1 (ClinVar).

How common is RAPSN p.Phe65= (c.195C>T) in the general population?

RAPSN p.Phe65= (c.195C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

RAPSN p.Phe65=

c.195C>T · rs772563068 · VCV716518

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

congenital myasthenic syndrome 11

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.31 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.56	GERP -3.9
Overall
CADD	4.356	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00142%

Overall 0.00205% 33/1,610,496 alleles · ultra-rare exomes 32/1,458,402 · genomes 1/152,094 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.0032%	31,229
European (non-Finnish)	0.00237%	42,141
Admixed American	0.00167%	59,986
Finnishnot grpmax-eligible	0.00165%	60,662

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.Phe65=
Coding: c.195C>T
MANE Select: NM_005055
dbSNP: rs772563068
Type: single nucleotide variant
Location: chr11:47448148 (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 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-phe65 (accessed [today's date]).

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