Is SP110 p.Cys577= (c.1731C>T) pathogenic?

SP110 p.Cys577= (c.1731C>T) is classified Benign in SP110 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-04). Common (popmax 12.4%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with hepatic veno-occlusive disease-immunodeficiency syndrome.

What condition is associated with SP110 p.Cys577= (c.1731C>T)?

SP110 p.Cys577= (c.1731C>T) is associated with hepatic veno-occlusive disease-immunodeficiency syndrome (ClinVar).

SP110 p.Cys577=

Q: How common is SP110 p.Cys577= (c.1731C>T) in the general population?

SP110 p.Cys577= (c.1731C>T) is common (popmax 12.4%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

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.1731C>T · rs13018234 · VCV334898

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 12.4%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

hepatic veno-occlusive disease-immunodeficiency syndrome

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 0.91	GERP 1.9, phastCons 0.9
Overall
CADD	14.76	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 12.4% European (non-Finnish) · 145,240/1,175,022 alleles

Filtering AF 12.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 12.3%

Overall 11.2% 179,390/1,608,768 alleles · common exomes 163,971/1,456,482 · genomes 15,419/152,286 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	12.4%	8
Middle Eastern	11.6%	9
Remaining individualsnot grpmax-eligible	10.6%	9
Amishnot grpmax-eligible	10.3%	10
Ashkenazi Jewishnot grpmax-eligible	9.64%	10
Finnishnot grpmax-eligible	9.08%	11
African / African-American	8.84%	11
Admixed American	8.49%	12
South Asian	6.95%	14
East Asian	0.058%	1,726

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.Cys577=
Coding: c.1731C>T
MANE Select: NM_080424
dbSNP: rs13018234
Type: single nucleotide variant
Location: chr2:230172150 (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 c.1888-2A>G Likely pathogenic ★★ same condition
SP110 p.Arg344Ter Pathogenic/Likely pathogenic ★★ same condition
SP110 p.Arg421Ter Pathogenic/Likely pathogenic ★★ same condition
SP110 p.Arg448Ter Pathogenic/Likely pathogenic ★★ same condition
SP110 p.Arg554Ter Pathogenic/Likely pathogenic ★★ same condition
SP110 p.Arg631Ter Pathogenic/Likely pathogenic ★★ same condition
SP110 c.1591-6T>G Uncertain significance ★★ same condition
SP110 c.583+3G>A Uncertain significance ★★ 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-cys577 (accessed [today's date]).

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