Is SP110 p.Ser304Phe (c.911C>T) pathogenic?

SP110 p.Ser304Phe (c.911C>T) is classified Uncertain significance in SP110 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-01-23). AlphaMissense: likely benign (0.19); Absent from gnomAD v4.1; Associated with hepatic veno-occlusive disease-immunodeficiency syndrome.

What condition is associated with SP110 p.Ser304Phe (c.911C>T)?

SP110 p.Ser304Phe (c.911C>T) is associated with hepatic veno-occlusive disease-immunodeficiency syndrome (ClinVar).

How common is SP110 p.Ser304Phe (c.911C>T) in the general population?

SP110 p.Ser304Phe (c.911C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SP110 p.Ser304Phe (c.911C>T)?

AlphaMissense predicts likely benign (score 0.19) — an in-silico prediction, not a clinical call.

SP110 p.Ser304Phe

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.911C>T · rs2043304942 · VCV1036082

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.19 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hepatic veno-occlusive disease-immunodeficiency syndrome

Computational evidence

Protein change
AlphaMissense	0.19	likely benign
REVEL	0.102	moderately benign-leaning
SaProt	LLR -9.18	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP 0.5, phastCons 0.001
Regional constraint	o/e 0.92	unconstrained · MANE · 48 kb · p 0.016 · regional, not allelic
Overall
CADD	16.55	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SP110
Protein: p.Ser304Phe
Coding: c.911C>T
MANE Select: NM_080424
dbSNP: rs2043304942
Type: single nucleotide variant
Location: chr2:230202716 (GRCh38)
Gene constraint: LOEUF 0.826 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.63
Residue 304: the 'disordered' region

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-ser304phe (accessed [today's date]).

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