Is SUFU p.Ile433= (c.1299T>C) pathogenic?

SUFU p.Ile433= (c.1299T>C) is classified Benign/Likely benign in SUFU (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-04). Common (popmax 44.3%, eas) — too common for a highly-penetrant pathogenic allele; Associated with nevoid basal cell carcinoma syndrome.

What condition is associated with SUFU p.Ile433= (c.1299T>C)?

SUFU p.Ile433= (c.1299T>C) is associated with nevoid basal cell carcinoma syndrome, medulloblastoma, familial meningioma (ClinVar).

SUFU p.Ile433=

Q: How common is SUFU p.Ile433= (c.1299T>C) in the general population?

SUFU p.Ile433= (c.1299T>C) is common (popmax 44.3%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1299T>C · rs17114803 · VCV260687

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Common

common (popmax 44.3%, eas) — too common for a highly-penetrant pathogenic allele

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 2.8	GERP 0.21, phastCons 1
Overall
CADD	12.17	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 44.3% East Asian · 19,880/44,868 alleles

Filtering AF 43.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 43.6%

Overall 11.4% 184,674/1,613,514 alleles · common exomes 161,590/1,461,254 · genomes 23,084/152,260 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	44.3%	2
Admixed American	24.4%	4
South Asian	22.6%	4
African / African-American	22%	5
Remaining individualsnot grpmax-eligible	12.5%	8
Amishnot grpmax-eligible	12.2%	8
Middle Eastern	11%	9
European (non-Finnish)	8.29%	12
Finnishnot grpmax-eligible	7.48%	13
Ashkenazi Jewishnot grpmax-eligible	6.75%	15

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.Ile433=
Coding: c.1299T>C
MANE Select: NM_016169
dbSNP: rs17114803
Type: single nucleotide variant
Location: chr10:102627177 (GRCh38)
Gene constraint: LOEUF 0.214 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.95 · 10 PDB
Residue 433: a UniProt-annotated variant site (sequence variant); a β-strand

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 familial meningioma hereditary neoplastic syndrome

Similar variants

SUFU p.Ile433Val Likely benign ★ 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
SUFU p.Arg299Ter Pathogenic ★★ same condition
SUFU p.Trp214Ter 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-ile433 (accessed [today's date]).

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