Is SP110 p.Ser79= (c.237T>G) pathogenic?

SP110 p.Ser79= (c.237T>G) is classified Conflicting classifications of pathogenicity in SP110 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-09-28). Ultra-rare (popmax 0.0181%, nfe); Associated with hepatic veno-occlusive disease-immunodeficiency syndrome.

What condition is associated with SP110 p.Ser79= (c.237T>G)?

SP110 p.Ser79= (c.237T>G) is associated with hepatic veno-occlusive disease-immunodeficiency syndrome (ClinVar).

How common is SP110 p.Ser79= (c.237T>G) in the general population?

SP110 p.Ser79= (c.237T>G) is ultra-rare (popmax 0.0181%, nfe) (gnomAD).

SP110 p.Ser79=

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.237T>G · rs202135641 · VCV334919

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0181%, 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.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -12	GERP -3.9
Overall
CADD	0.299	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0181% European (non-Finnish) · 214/1,179,426 alleles

Filtering AF 0.0161% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0153%

Overall 0.0143% 231/1,613,454 alleles · ultra-rare exomes 221/1,461,212 · genomes 10/152,242 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0181%	5,511
Remaining individualsnot grpmax-eligible	0.0112%	8,924
Admixed American	0.01%	10,002
African / African-American	0.00534%	18,732

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.Ser79=
Coding: c.237T>G
MANE Select: NM_080424
dbSNP: rs202135641
Type: single nucleotide variant
Location: chr2:230215029 (GRCh38)
Gene constraint: LOEUF 0.826 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.63
Residue 79: the hsr domain

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-ser79 (accessed [today's date]).

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