Is SUFU p.Arg298Pro (c.893G>C) pathogenic?

SUFU p.Arg298Pro (c.893G>C) is classified Uncertain significance in SUFU (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-10). AlphaMissense: ambiguous (0.5267); Absent from gnomAD v4.1; Associated with nevoid basal cell carcinoma syndrome.

What condition is associated with SUFU p.Arg298Pro (c.893G>C)?

SUFU p.Arg298Pro (c.893G>C) is associated with nevoid basal cell carcinoma syndrome, medulloblastoma (ClinVar).

How common is SUFU p.Arg298Pro (c.893G>C) in the general population?

SUFU p.Arg298Pro (c.893G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SUFU p.Arg298Pro (c.893G>C)?

AlphaMissense predicts ambiguous (score 0.5267) — an in-silico prediction, not a clinical call.

SUFU p.Arg298Pro

c.893G>C · VCV3756752

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5267 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

nevoid basal cell carcinoma syndrome

Computational evidence

Protein change
AlphaMissense	0.5267	ambiguous
REVEL	0.285	benign-leaning
SaProt	LLR -6.20	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.9, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 126 kb · p 5.7e-14 · regional, not allelic
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

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.Arg298Pro
Coding: c.893G>C
MANE Select: NM_016169
Type: single nucleotide variant
Location: chr10:102597276 (GRCh38)
Gene constraint: LOEUF 0.214 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.95 · 10 PDB
Residue 298: 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

Similar variants

SUFU p.Arg298Gln Uncertain significance ★★ ⚠ same residue
SUFU p.Arg298Gly Uncertain significance ★★ same residue
SUFU p.Arg298Trp Uncertain significance ★★ same residue
SUFU p.Arg298fs Pathogenic ★ same residue
SUFU p.Arg298Leu Uncertain significance ★ same residue
SUFU p.Arg298= Likely benign ★ same residue
SUFU c.1022+1G>A Pathogenic ★★ same condition
SUFU c.1023-2A>T 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-arg298pro (accessed [today's date]).

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