Is RPSA p.Pro199fs (c.590_594dup) pathogenic?

RPSA p.Pro199fs (c.590594dup) is classified Pathogenic in RPSA (ClinVar, No assertion criteria, 1 submitter; last evaluated 2013-05-24). Absent from gnomAD; Associated with familial isolated congenital asplenia.

What condition is associated with RPSA p.Pro199fs (c.590_594dup)?

RPSA p.Pro199fs (c.590_594dup) is associated with familial isolated congenital asplenia (ClinVar).

How common is RPSA p.Pro199fs (c.590_594dup) in the general population?

RPSA p.Pro199fs (c.590_594dup) is absent from gnomAD (gnomAD).

RPSA p.Pro199fs

c.590_594dup · rs398122389 · VCV64672

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

familial isolated congenital asplenia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 5 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.29	GERP -3.1, phastCons 0.95

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: RPSA
Protein: p.Pro199fs
Coding: c.590_594dup
MANE Select: NM_002295
dbSNP: rs398122389
Type: Duplication
Location: chr3:39411738 (GRCh38)
Gene constraint: LOEUF 0.144 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.45 · 204 PDB
Residue 199: an α-helix

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

Disease context

familial isolated congenital asplenia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RPSA c.134-32C>T Benign ★★ same condition
RPSA c.-8T>C Benign/Likely benign ★★ same condition
RPSA p.Leu173= Benign/Likely benign ★★ same condition
RPSA p.Arg180Trp Pathogenic ★ same condition
RPSA p.Arg186Cys Likely pathogenic ★ same condition
RPSA p.Asn165Tyr Likely pathogenic ★ same condition
RPSA p.Lys220fs Likely pathogenic ★ same condition
RPSA c.498+8T>A Conflicting classifications of pathogenicity ★ 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/rpsa-p-pro199fs (accessed [today's date]).

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