Is RAPSN p.Pro381= (c.1143T>C) pathogenic?

RAPSN p.Pro381= (c.1143T>C) is classified Benign in RAPSN (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-06-12). Common (popmax 76.8%, sas) — too common for a highly-penetrant pathogenic allele; Associated with fetal akinesia deformation sequence 2.

What condition is associated with RAPSN p.Pro381= (c.1143T>C)?

RAPSN p.Pro381= (c.1143T>C) is associated with fetal akinesia deformation sequence 2, congenital myasthenic syndrome 11, congenital myasthenic syndrome (ClinVar).

RAPSN p.Pro381=

Q: How common is RAPSN p.Pro381= (c.1143T>C) in the general population?

RAPSN p.Pro381= (c.1143T>C) is common (popmax 76.8%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1143T>C · rs7126210 · VCV130089

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

gnomAD v4.1

Common

common (popmax 76.8%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

fetal akinesia deformation sequence 2

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 -0.018	GERP -2, phastCons 0.42
Overall
CADD	6.641	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 76.8% South Asian · 65,194/84,848 alleles

Filtering AF 76.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 76.1%

Overall 69.5% 1,086,404/1,562,730 alleles · common exomes 991,432/1,410,724 · genomes 94,972/152,006 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	86.8%	1
South Asiangrpmax	76.8%	1
Middle Eastern	74.1%	1
Ashkenazi Jewishnot grpmax-eligible	71.9%	1
European (non-Finnish)	71.7%	1
Remaining individualsnot grpmax-eligible	70.7%	1
Admixed American	63.4%	2
Finnishnot grpmax-eligible	62%	2
East Asian	60.1%	2
African / African-American	41.3%	2

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro381=
Coding: c.1143T>C
MANE Select: NM_005055
dbSNP: rs7126210
Type: single nucleotide variant
Location: chr11:47438755 (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 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: congenital myasthenic syndrome 11 congenital myasthenic syndrome 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-pro381 (accessed [today's date]).

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