Is SUFU p.Phe197= (c.591C>T) pathogenic?

SUFU p.Phe197= (c.591C>T) is classified Likely benign in SUFU (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-27). Very rare (popmax 0.00186%, nfe); Associated with nevoid basal cell carcinoma syndrome.

What condition is associated with SUFU p.Phe197= (c.591C>T)?

SUFU p.Phe197= (c.591C>T) is associated with nevoid basal cell carcinoma syndrome, medulloblastoma, hereditary neoplastic syndrome (ClinVar).

How common is SUFU p.Phe197= (c.591C>T) in the general population?

SUFU p.Phe197= (c.591C>T) is very rare (popmax 0.00186%, nfe) (gnomAD).

SUFU p.Phe197=

c.591C>T · rs748830496 · VCV826056

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00186%, nfe)

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 0.4	GERP -0.36, phastCons 0.99
Overall
CADD	7.926	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00186% European (non-Finnish) · 22/1,180,040 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00157% 23/1,461,706 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00186%	53,638
Remaining individualsnot grpmax-eligible	0.0016%	62,510

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.Phe197=
Coding: c.591C>T
MANE Select: NM_016169
dbSNP: rs748830496
Type: single nucleotide variant
Location: chr10:102592718 (GRCh38)
Gene constraint: LOEUF 0.214 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.95 · 10 PDB
Residue 197: 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 hereditary neoplastic syndrome

Similar variants

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
SUFU p.Trp88Ter Pathogenic/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-phe197 (accessed [today's date]).

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