Is SPEN p.Pro2055fs (c.6164del) pathogenic?

SPEN p.Pro2055fs (c.6164del) is classified Pathogenic in SPEN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-09). Absent from gnomAD; Associated with Radio-Tartaglia syndrome.

What condition is associated with SPEN p.Pro2055fs (c.6164del)?

SPEN p.Pro2055fs (c.6164del) is associated with Radio-Tartaglia syndrome (ClinVar).

How common is SPEN p.Pro2055fs (c.6164del) in the general population?

SPEN p.Pro2055fs (c.6164del) is absent from gnomAD (gnomAD).

SPEN p.Pro2055fs

c.6164del · rs767964268 · VCV2691008

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Radio-Tartaglia syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 11 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1	GERP -3.6

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SPEN
Protein: p.Pro2055fs
Coding: c.6164del
MANE Select: NM_015001
dbSNP: rs767964268
Type: Deletion
Location: chr1:15932399 (GRCh38)
Gene constraint: LOEUF 0.094 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2055: a UniProt-annotated variant site (in ratars); a UniProt-annotated variant site (in ratars; uncertain significance); the 'disordered' region

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

Disease context

Radio-Tartaglia syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SPEN p.Glu2029fs Pathogenic/Likely pathogenic ★★ same condition
SPEN p.Glu2214fs Pathogenic/Likely pathogenic ★★ same condition
SPEN p.Ser2075fs Pathogenic ★★ same condition
SPEN p.Ala307fs Likely pathogenic ★ same condition
SPEN p.Arg1418fs Likely pathogenic ★ same condition
SPEN p.Asp649fs Likely pathogenic ★ same condition
SPEN p.Glu996fs Likely pathogenic ★ same condition
SPEN p.Gly2372fs Pathogenic ★ 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-pro2055fs (accessed [today's date]).

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