Is SUFU p.Phe439Ser (c.1316T>C) pathogenic?

SUFU p.Phe439Ser (c.1316T>C) is classified Uncertain significance in SUFU (ClinVar, Single submitter, 1 submitter; last evaluated 2017-10-23). AlphaMissense: likely pathogenic (0.8598); Absent from gnomAD v4.1; Associated with nevoid basal cell carcinoma syndrome.

What condition is associated with SUFU p.Phe439Ser (c.1316T>C)?

SUFU p.Phe439Ser (c.1316T>C) is associated with nevoid basal cell carcinoma syndrome, medulloblastoma (ClinVar).

How common is SUFU p.Phe439Ser (c.1316T>C) in the general population?

SUFU p.Phe439Ser (c.1316T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SUFU p.Phe439Ser (c.1316T>C)?

AlphaMissense predicts likely pathogenic (score 0.8598) — an in-silico prediction, not a clinical call.

SUFU p.Phe439Ser

c.1316T>C · rs778975698 · VCV524657

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8598 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

nevoid basal cell carcinoma syndrome

Computational evidence

Protein change
AlphaMissense	0.8598	likely pathogenic
REVEL	0.536	indeterminate
SaProt	LLR -6.88	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.4, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 126 kb · p 5.7e-14 · regional, not allelic
Overall
CADD	24.4	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.Phe439Ser
Coding: c.1316T>C
MANE Select: NM_016169
dbSNP: rs778975698
Type: single nucleotide variant
Location: chr10:102627194 (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

nevoid basal cell carcinoma syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: medulloblastoma

Similar variants

SUFU p.Phe439= 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-phe439ser (accessed [today's date]).

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