Is SUFU p.Pro382Arg (c.1145C>G) pathogenic?

SUFU p.Pro382Arg (c.1145C>G) is classified Uncertain significance in SUFU (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-05). AlphaMissense: likely pathogenic (0.8812); Absent from gnomAD v4.1; Associated with medulloblastoma.

What condition is associated with SUFU p.Pro382Arg (c.1145C>G)?

SUFU p.Pro382Arg (c.1145C>G) is associated with medulloblastoma, nevoid basal cell carcinoma syndrome (ClinVar).

How common is SUFU p.Pro382Arg (c.1145C>G) in the general population?

SUFU p.Pro382Arg (c.1145C>G) is absent from gnomAD v4.1 (gnomAD).

How is Medulloblastoma inherited?

Typically Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about SUFU p.Pro382Arg (c.1145C>G)?

AlphaMissense predicts likely pathogenic (score 0.8812) — an in-silico prediction, not a clinical call.

SUFU p.Pro382Arg

c.1145C>G · rs1401882800 · VCV2952545

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8812 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

medulloblastoma

Computational evidence

Protein change
AlphaMissense	0.8812	likely pathogenic
REVEL	0.573	indeterminate
SaProt	LLR -12.45	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.7, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 126 kb · p 5.7e-14 · regional, not allelic
Overall
CADD	28.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Pro382Arg
Coding: c.1145C>G
MANE Select: NM_016169
dbSNP: rs1401882800
Type: single nucleotide variant
Location: chr10:102615390 (GRCh38)
Gene constraint: LOEUF 0.214 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.95 · 10 PDB
Residue 382: a UniProt-annotated variant site (sequence variant); a UniProt-annotated variant site (in)

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

Disease context

medulloblastoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: nevoid basal cell carcinoma syndrome

For Medulloblastoma (Orphanet):

Inheritance: Not applicable
Onset: All ages
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

SUFU p.Pro382Leu Uncertain significance ★★ ⚠ same residue
SUFU p.Pro382= Likely benign ★★ same residue
SUFU p.Pro382Ser Uncertain significance ★ ⚠ 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
SUFU p.Arg146Ter 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-pro382arg (accessed [today's date]).

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