Is SUFU p.Pro281= (c.843C>A) pathogenic?

SUFU p.Pro281= (c.843C>A) is classified Likely benign in SUFU (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-10). Absent from gnomAD v4.1; Associated with nevoid basal cell carcinoma syndrome.

What condition is associated with SUFU p.Pro281= (c.843C>A)?

SUFU p.Pro281= (c.843C>A) is associated with nevoid basal cell carcinoma syndrome, medulloblastoma, hereditary neoplastic syndrome (ClinVar).

How common is SUFU p.Pro281= (c.843C>A) in the general population?

SUFU p.Pro281= (c.843C>A) is absent from gnomAD v4.1 (gnomAD).

SUFU p.Pro281=

c.843C>A · rs1590066015 · VCV1115591

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

nevoid basal cell carcinoma syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.21	GERP -5.9, phastCons 0.32
Overall
CADD	3.792	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SUFU
Protein: p.Pro281=
Coding: c.843C>A
MANE Select: NM_016169
dbSNP: rs1590066015
Type: single nucleotide variant
Location: chr10:102597226 (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

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.Pro281Ser Uncertain significance ★★ ⚠ same residue
SUFU p.Pro281Thr Uncertain significance ★★ ⚠ 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.683+1G>A 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-pro281 (accessed [today's date]).

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