Is SP110 p.Ser462Pro (c.1384T>C) pathogenic?

SP110 p.Ser462Pro (c.1384T>C) is classified Conflicting classifications of pathogenicity in SP110 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-02-19). AlphaMissense: likely benign (0.0792); Very rare (popmax 0.0011%, sas); Associated with Inborn genetic diseases.

What condition is associated with SP110 p.Ser462Pro (c.1384T>C)?

SP110 p.Ser462Pro (c.1384T>C) is associated with Inborn genetic diseases, hepatic veno-occlusive disease-immunodeficiency syndrome (ClinVar).

How common is SP110 p.Ser462Pro (c.1384T>C) in the general population?

SP110 p.Ser462Pro (c.1384T>C) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about SP110 p.Ser462Pro (c.1384T>C)?

AlphaMissense predicts likely benign (score 0.0792) — an in-silico prediction, not a clinical call.

SP110 p.Ser462Pro

c.1384T>C · rs2469459667 · VCV3167863

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0792 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0792	likely benign
REVEL	0.023	moderately benign-leaning
SaProt	LLR -5.19	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 1.6	GERP -0.18, phastCons 0.19
Regional constraint	o/e 0.92	unconstrained · MANE · 48 kb · p 0.016 · regional, not allelic
Overall
CADD	4.028	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,040 alleles

Overall 6.2e-05% 1/1,613,606 alleles · very rare exomes 1/1,461,288 · genomes 0/152,318 · 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.Ser462Pro
Coding: c.1384T>C
MANE Select: NM_080424
dbSNP: rs2469459667
Type: single nucleotide variant
Location: chr2:230178220 (GRCh38)
Gene constraint: LOEUF 0.826 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.63
Residue 462: the sand domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hepatic veno-occlusive disease-immunodeficiency syndrome

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-ser462pro (accessed [today's date]).

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