Is SPSB3 p.Ser80Phe (c.239C>T) pathogenic?

SPSB3 p.Ser80Phe (c.239C>T) is classified Likely benign in SPSB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-04). AlphaMissense: likely benign (0.1146); Low-frequency (popmax 1.02%, afr).

How common is SPSB3 p.Ser80Phe (c.239C>T) in the general population?

SPSB3 p.Ser80Phe (c.239C>T) is low-frequency (popmax 1.02%, afr) (gnomAD).

What do computational predictors say about SPSB3 p.Ser80Phe (c.239C>T)?

AlphaMissense predicts likely benign (score 0.1146) — an in-silico prediction, not a clinical call.

SPSB3 p.Ser80Phe

c.239C>T · VCV4174182

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1146 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.02%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1146	likely benign
REVEL	0.145	moderately benign-leaning
SaProt	LLR -7.99	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 6.8	GERP 1.5, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 4,383 bp · p 0.15 · regional, not allelic
Overall
CADD	22.7	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 1.02% African / African-American · 766/75,050 alleles

Filtering AF 0.961% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.937%

Overall 0.0561% 904/1,612,082 alleles · low-frequency exomes 469/1,459,736 · genomes 435/152,346 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.02%	98
Remaining individualsnot grpmax-eligible	0.104%	961
Admixed American	0.0717%	1,395
Middle Eastern	0.0509%	1,965
South Asian	0.022%	4,553
European (non-Finnish)	0.000593%	168,522

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: SPSB3
Protein: p.Ser80Phe
Coding: c.239C>T
MANE Select: NM_080861
Type: single nucleotide variant
Location: chr16:1778500 (GRCh38)
Gene constraint: LOEUF 0.925 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.01 · 2 PDB

Full SPSB3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SPSB3 p.Ser80Tyr Uncertain significance ★ ⚠ same residue
SPSB3 p.Ala115= Benign ★★ same type
SPSB3 p.Ala18Val Uncertain significance ★ ⚠ same type
SPSB3 p.Ala22Thr Uncertain significance ★ ⚠ same type
SPSB3 p.Ala274Ser Uncertain significance ★ ⚠ same type
SPSB3 p.Ala334Val Uncertain significance ★ ⚠ same type
SPSB3 p.Ala337Thr Uncertain significance ★ ⚠ same type
SPSB3 p.Arg20Gly Uncertain significance ★ ⚠ same type

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/spsb3-p-ser80phe (accessed [today's date]).

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