Is SP110 p.Pro564fs (c.1691del) pathogenic?

SP110 p.Pro564fs (c.1691del) is classified Pathogenic in SP110 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-07). Very rare (popmax 8.48e-05%, nfe); Associated with hepatic veno-occlusive disease-immunodeficiency syndrome.

What condition is associated with SP110 p.Pro564fs (c.1691del)?

SP110 p.Pro564fs (c.1691del) is associated with hepatic veno-occlusive disease-immunodeficiency syndrome (ClinVar).

How common is SP110 p.Pro564fs (c.1691del) in the general population?

SP110 p.Pro564fs (c.1691del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

SP110 p.Pro564fs

Q: How is Hepatic veno-occlusive disease-immunodeficiency syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1691del · rs1245290762 · VCV971546

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

hepatic veno-occlusive disease-immunodeficiency syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 15 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -9.9	GERP -3.9

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,178,922 alleles

Overall 6.2e-05% 1/1,612,918 alleles · very rare exomes 1/1,460,676 · genomes 0/152,242 · joint denominator

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: SP110
Protein: p.Pro564fs
Coding: c.1691del
MANE Select: NM_080424
dbSNP: rs1245290762
Type: Deletion
Location: chr2:230172859 (GRCh38)
Gene constraint: LOEUF 0.826 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.63

Full SP110 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hepatic veno-occlusive disease-immunodeficiency syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hepatic veno-occlusive disease-immunodeficiency syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

SP110 p.Arg373fs Pathogenic/Likely pathogenic ★★ same condition
SP110 p.Ser215fs Pathogenic ★★ same condition
SP110 p.His589fs Likely pathogenic ★ same condition
SP110 p.Leu645fs Pathogenic ★ same condition
SP110 p.Lys453_Ser454insTer Pathogenic ★ same condition
SP110 p.Ser296fs Pathogenic ★ same condition
SP110 p.Val315fs Pathogenic ★ same condition
SP110 p.Val591_Ser592insTer 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/sp110-p-pro564fs (accessed [today's date]).

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