Is SP110 p.Val504= (c.1512C>T) pathogenic?

SP110 p.Val504= (c.1512C>T) is classified Likely benign in SP110 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-03). Ultra-rare (popmax 0.034%, sas); Associated with hepatic veno-occlusive disease-immunodeficiency syndrome.

What condition is associated with SP110 p.Val504= (c.1512C>T)?

SP110 p.Val504= (c.1512C>T) is associated with hepatic veno-occlusive disease-immunodeficiency syndrome (ClinVar).

How common is SP110 p.Val504= (c.1512C>T) in the general population?

SP110 p.Val504= (c.1512C>T) is ultra-rare (popmax 0.034%, sas) (gnomAD).

SP110 p.Val504=

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.1512C>T · rs547650308 · VCV1455994

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.034%, sas)

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 -6.7	GERP -3.6
Overall
CADD	0.04	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.034% South Asian · 31/91,072 alleles

Filtering AF 0.0246% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0214%

Overall 0.00248% 40/1,613,780 alleles · ultra-rare exomes 38/1,461,692 · genomes 2/152,088 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.034%	2,938
Remaining individualsnot grpmax-eligible	0.0032%	31,249
East Asian	0.00223%	44,884
European (non-Finnish)	0.000509%	196,638

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.Val504=
Coding: c.1512C>T
MANE Select: NM_080424
dbSNP: rs547650308
Type: single nucleotide variant
Location: chr2:230177616 (GRCh38)
Gene constraint: LOEUF 0.826 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.63
Residue 504: the sand 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-val504 (accessed [today's date]).

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