Is SUFU p.Pro281fs (c.841_842delinsA) pathogenic?

SUFU p.Pro281fs (c.841842delinsA) is classified Likely pathogenic in SUFU (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-03). Associated with basal cell nevus syndrome 2.

What condition is associated with SUFU p.Pro281fs (c.841_842delinsA)?

SUFU p.Pro281fs (c.841_842delinsA) is associated with basal cell nevus syndrome 2 (ClinVar).

SUFU p.Pro281fs

c.841_842delinsA · VCV4759327

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

basal cell nevus syndrome 2

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 7 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.9, phastCons 1

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

Variant & gene context

Gene: SUFU
Protein: p.Pro281fs
Coding: c.841_842delinsA
MANE Select: NM_016169
Type: Indel
Location: chr10:102597224 (GRCh38)
Gene constraint: LOEUF 0.214 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.95 · 10 PDB
Residue 281: the 'disordered' region

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

Disease context

basal cell nevus syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SUFU p.Pro281Ser Uncertain significance ★★ ⚠ same residue
SUFU p.Pro281Thr Uncertain significance ★★ ⚠ same residue
SUFU p.Pro281= Likely benign ★★ same residue
SUFU p.Pro281Ala Uncertain significance ★ ⚠ same residue
SUFU p.Pro281Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
SUFU c.1022+1G>A Pathogenic ★★ same condition
SUFU c.1023-2A>T Likely pathogenic ★★ same condition
SUFU c.684-2A>G Likely 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/sufu-p-pro281fs (accessed [today's date]).

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