Is SP110 p.Arg91Ser (c.271C>A) pathogenic?

SP110 p.Arg91Ser (c.271C>A) is classified Uncertain significance in SP110 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-21). AlphaMissense: ambiguous (0.4025); Ultra-rare (popmax 0.0285%, sas); Associated with Inborn genetic diseases.

What condition is associated with SP110 p.Arg91Ser (c.271C>A)?

SP110 p.Arg91Ser (c.271C>A) is associated with Inborn genetic diseases, hepatic veno-occlusive disease-immunodeficiency syndrome (ClinVar).

How common is SP110 p.Arg91Ser (c.271C>A) in the general population?

SP110 p.Arg91Ser (c.271C>A) is ultra-rare (popmax 0.0285%, sas) (gnomAD).

What do computational predictors say about SP110 p.Arg91Ser (c.271C>A)?

AlphaMissense predicts ambiguous (score 0.4025) — an in-silico prediction, not a clinical call.

SP110 p.Arg91Ser

c.271C>A · rs201053153 · VCV656709

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4025 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0285%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4025	ambiguous
REVEL	0.607	indeterminate
SaProt	LLR -8.57	tolerated
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.021	GERP -3.9
Regional constraint	o/e 0.92	unconstrained · MANE · 48 kb · p 0.016 · regional, not allelic
Overall
CADD	6.338	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 0.0285% South Asian · 26/91,076 alleles

Filtering AF 0.0199% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0171%

Overall 0.00347% 56/1,613,832 alleles · ultra-rare exomes 50/1,461,568 · genomes 6/152,264 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0285%	3,503
European (non-Finnish)	0.00246%	40,681
Remaining individualsnot grpmax-eligible	0.0016%	62,498

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.Arg91Ser
Coding: c.271C>A
MANE Select: NM_080424
dbSNP: rs201053153
Type: single nucleotide variant
Location: chr2:230214995 (GRCh38)
Gene constraint: LOEUF 0.826 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.63
Residue 91: the hsr 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-arg91ser (accessed [today's date]).

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