Is SUFU p.Ser342fs (c.1022dup) pathogenic?

SUFU p.Ser342fs (c.1022dup) is classified Likely pathogenic in SUFU (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-31). Ultra-rare (gnomAD MAF 7.136e-07); Associated with nevoid basal cell carcinoma syndrome.

What condition is associated with SUFU p.Ser342fs (c.1022dup)?

SUFU p.Ser342fs (c.1022dup) is associated with nevoid basal cell carcinoma syndrome (ClinVar).

How common is SUFU p.Ser342fs (c.1022dup) in the general population?

SUFU p.Ser342fs (c.1022dup) is ultra-rare (gnomAD MAF 7.136e-07) (gnomAD).

SUFU p.Ser342fs

c.1022dup · rs2135889249 · VCV1691869

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (gnomAD MAF 7.136e-07)

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

dbSNP / gnomAD

Global frequency 7.14e-05% via dbSNP · ultra-rare

No ancestry breakdown or filtering allele frequency is available for this variant, so BA1/BS1 cannot be assessed from this figure alone.

Variant & gene context

Gene: SUFU
Protein: p.Ser342fs
Coding: c.1022dup
MANE Select: NM_016169
dbSNP: rs2135889249
Type: Duplication
Location: chr10:102599540 (GRCh38)
Gene constraint: LOEUF 0.214 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.95 · 10 PDB
Residue 342: the 'disordered' region; a UniProt-annotated variant site (sequence variant); a modified residue (phosphoserine)

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

Similar variants

SUFU p.Ser342Ile Uncertain significance ★★ ⚠ same residue
SUFU p.Ser342Arg Uncertain significance ★ ⚠ same residue
SUFU p.Thr196fs Pathogenic ★★ same condition
SUFU p.Leu312_Arg313insLeu Uncertain significance ★★ same condition
SUFU p.Arg42fs Pathogenic ★ same condition
SUFU p.Cys273fs Pathogenic ★ same condition
SUFU p.Gly193fs Pathogenic ★ same condition
SUFU p.Phe417fs 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-ser342fs (accessed [today's date]).

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