Is SUFU p.Pro341fs (c.1022del) pathogenic?

SUFU p.Pro341fs (c.1022del) is classified Pathogenic in SUFU (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-11-07). Very rare (popmax 8.48e-05%, nfe); Associated with nevoid basal cell carcinoma syndrome.

What condition is associated with SUFU p.Pro341fs (c.1022del)?

SUFU p.Pro341fs (c.1022del) is associated with nevoid basal cell carcinoma syndrome, medulloblastoma, hereditary neoplastic syndrome (ClinVar).

How common is SUFU p.Pro341fs (c.1022del) in the general population?

SUFU p.Pro341fs (c.1022del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

SUFU p.Pro341fs

c.1022del · rs2135889249 · VCV2562345

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

nevoid basal cell carcinoma 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 8 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.1	GERP -2.8, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,918 alleles

Overall 6.2e-05% 1/1,614,014 alleles · very rare exomes 1/1,461,700 · genomes 0/152,314 · joint denominator

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: SUFU
Protein: p.Pro341fs
Coding: c.1022del
MANE Select: NM_016169
dbSNP: rs2135889249
Type: Deletion
Location: chr10:102599541 (GRCh38)
Gene constraint: LOEUF 0.214 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.95 · 10 PDB
Residue 341: the 'disordered' region; a UniProt-annotated variant site (sequence variant); a UniProt-annotated variant site (found in a patient with holoprosencephaly; uncertain significance)

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

Disease context

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

Also linked: medulloblastoma hereditary neoplastic syndrome

Similar variants

SUFU p.Pro341Ala Uncertain significance ★★ ⚠ same residue
SUFU p.Pro341Arg Uncertain significance ★ ⚠ same residue
SUFU p.Pro341Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
SUFU p.Pro341Ser Uncertain significance ★ ⚠ same residue
SUFU p.Pro341= Likely benign ★ same residue
SUFU p.Ala340fs Pathogenic ★★ same condition
SUFU p.Gln375fs Pathogenic ★★ same condition
SUFU p.Glu438fs Pathogenic/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-pro341fs (accessed [today's date]).

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