Is SPEN p.Ser3528= (c.10584T>C) pathogenic?

SPEN p.Ser3528= (c.10584T>C) is classified Likely benign in SPEN (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-15). Absent from gnomAD v4.1; Associated with SPEN-related disorder.

What condition is associated with SPEN p.Ser3528= (c.10584T>C)?

SPEN p.Ser3528= (c.10584T>C) is associated with SPEN-related disorder (ClinVar).

How common is SPEN p.Ser3528= (c.10584T>C) in the general population?

SPEN p.Ser3528= (c.10584T>C) is absent from gnomAD v4.1 (gnomAD).

SPEN p.Ser3528=

c.10584T>C · rs2523102495 · VCV3053874

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

SPEN-related disorder

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 -2.4	GERP -3.9
Overall
CADD	3.807	PHRED · no single calibrated threshold — expert panels disagree

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: SPEN
Protein: p.Ser3528=
Coding: c.10584T>C
MANE Select: NM_015001
dbSNP: rs2523102495
Type: single nucleotide variant
Location: chr1:15937886 (GRCh38)
Gene constraint: LOEUF 0.094 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 3528: a UniProt-annotated variant site (in ratars); a UniProt-annotated variant site (in ratars; uncertain significance); a β-strand; the spoc domain

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

Disease context

SPEN-related disorder

Similar variants

SPEN p.Arg2337Ter Likely pathogenic ★★ same condition
SPEN p.Trp2501Ter Pathogenic/Likely pathogenic ★★ same condition
SPEN p.Asp549Glu Uncertain significance ★★ same condition
SPEN p.Arg637Ter Likely pathogenic ★ same condition
SPEN p.Gln2855Ter Likely pathogenic ★ same condition
SPEN p.Ser283Ter Pathogenic ★ same condition
SPEN p.Ala2517Val Uncertain significance ★ ⚠ same condition
SPEN p.Ala2779Gly 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/spen-p-ser3528 (accessed [today's date]).

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