Is SUFU p.Asp66= (c.198C>T) pathogenic?

SUFU p.Asp66= (c.198C>T) is classified Likely benign in SUFU (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-27). Ultra-rare (popmax 0.0959%, afr); Associated with medulloblastoma.

What condition is associated with SUFU p.Asp66= (c.198C>T)?

SUFU p.Asp66= (c.198C>T) is associated with medulloblastoma, nevoid basal cell carcinoma syndrome, hereditary neoplastic syndrome (ClinVar).

How common is SUFU p.Asp66= (c.198C>T) in the general population?

SUFU p.Asp66= (c.198C>T) is ultra-rare (popmax 0.0959%, afr) (gnomAD).

How is Medulloblastoma inherited?

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

SUFU p.Asp66=

c.198C>T · rs189500468 · VCV241085

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0959%, afr)

Conditions

medulloblastoma

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 0.059	GERP -0.012, phastCons 0.91
Overall
CADD	7.593	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0959% African / African-American · 72/75,042 alleles

Filtering AF 0.0781% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0715%

Overall 0.011% 178/1,614,148 alleles · ultra-rare exomes 133/1,461,838 · genomes 45/152,310 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0959%	1,042
European (non-Finnish)	0.0083%	12,041
Admixed American	0.00666%	15,004
Remaining individualsnot grpmax-eligible	0.0064%	15,626

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.Asp66=
Coding: c.198C>T
MANE Select: NM_016169
dbSNP: rs189500468
Type: single nucleotide variant
Location: chr10:102509184 (GRCh38)
Gene constraint: LOEUF 0.214 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.95 · 10 PDB

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 hereditary neoplastic syndrome

For Medulloblastoma (Orphanet):

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

Similar variants

SUFU p.Asp66Tyr 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
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-asp66 (accessed [today's date]).

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