Is SUFU p.Phe439= (c.1317T>C) pathogenic?

SUFU p.Phe439= (c.1317T>C) is classified Likely benign in SUFU (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-06). Very rare (popmax 0.00833%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with SUFU p.Phe439= (c.1317T>C)?

SUFU p.Phe439= (c.1317T>C) is associated with hereditary neoplastic syndrome, nevoid basal cell carcinoma syndrome, medulloblastoma (ClinVar).

How common is SUFU p.Phe439= (c.1317T>C) in the general population?

SUFU p.Phe439= (c.1317T>C) is very rare (popmax 0.00833%, amr) (gnomAD).

SUFU p.Phe439=

c.1317T>C · rs748603932 · VCV790902

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Conditions

hereditary neoplastic 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 2.9	GERP 2.4, phastCons 1
Overall
CADD	9.526	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00833% Admixed American · 5/60,034 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00206%

Overall 0.000372% 6/1,614,230 alleles · very rare exomes 6/1,461,878 · genomes 0/152,352 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	12,007
European (non-Finnish)	8.47e-05%	1,180,027

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.Phe439=
Coding: c.1317T>C
MANE Select: NM_016169
dbSNP: rs748603932
Type: single nucleotide variant
Location: chr10:102627195 (GRCh38)
Gene constraint: LOEUF 0.214 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.95 · 10 PDB
Residue 439: a UniProt-annotated variant site (sequence variant); an α-helix

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: nevoid basal cell carcinoma syndrome medulloblastoma

Similar variants

SUFU p.Phe439Ser 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-phe439 (accessed [today's date]).

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