Is SPOP p.Pro367fs (c.1100del) pathogenic?

SPOP p.Pro367fs (c.1100del) is classified Uncertain significance in SPOP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-12). Absent from gnomAD; Associated with neurodevelopmental disorder with microcephaly and dysmorphic facies.

What condition is associated with SPOP p.Pro367fs (c.1100del)?

SPOP p.Pro367fs (c.1100del) is associated with neurodevelopmental disorder with microcephaly and dysmorphic facies (ClinVar).

How common is SPOP p.Pro367fs (c.1100del) in the general population?

SPOP p.Pro367fs (c.1100del) is absent from gnomAD (gnomAD).

SPOP p.Pro367fs

c.1100del · rs2143097814 · VCV3236580

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

neurodevelopmental disorder with microcephaly and dysmorphic facies

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 LoF-intolerant gene
NMD	escapes	premature termination codon in the last exon (10 of 10) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.12	GERP -0.14, phastCons 0.61

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: SPOP
Protein: p.Pro367fs
Coding: c.1100del
MANE Select: NM_001007228
dbSNP: rs2143097814
Type: Deletion
Location: chr17:49600403 (GRCh38)
Gene constraint: LOEUF 0.377 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 90.38 · 36 PDB

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

Disease context

neurodevelopmental disorder with microcephaly and dysmorphic facies — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SPOP p.Gly365fs Uncertain significance ★ same condition
SPOP p.Pro367= Likely benign ★ same residue
SPOP p.Arg121Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
SPOP p.Asp144Asn Pathogenic/Likely pathogenic ★★ ⚠ same condition
SPOP p.Thr260Met Uncertain significance ★★ ⚠ same condition
SPOP p.Phe104Leu Likely pathogenic ★ ⚠ same condition
SPOP p.Asn147Ser Uncertain significance ★ ⚠ same condition
SPOP p.Glu145Lys 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/spop-p-pro367fs (accessed [today's date]).

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