Is SUFU p.Pro357Ser (c.1069C>T) pathogenic?

SUFU p.Pro357Ser (c.1069C>T) is classified Uncertain significance in SUFU (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-15). AlphaMissense: likely pathogenic (0.6689); Very rare (popmax 0.000169%, nfe); Associated with nevoid basal cell carcinoma syndrome.

What condition is associated with SUFU p.Pro357Ser (c.1069C>T)?

SUFU p.Pro357Ser (c.1069C>T) is associated with nevoid basal cell carcinoma syndrome, medulloblastoma, hereditary neoplastic syndrome (ClinVar).

How common is SUFU p.Pro357Ser (c.1069C>T) in the general population?

SUFU p.Pro357Ser (c.1069C>T) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about SUFU p.Pro357Ser (c.1069C>T)?

AlphaMissense predicts likely pathogenic (score 0.6689) — an in-silico prediction, not a clinical call.

SUFU p.Pro357Ser

c.1069C>T · rs2135930032 · VCV1714246

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6689 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

nevoid basal cell carcinoma syndrome

Computational evidence

Protein change
AlphaMissense	0.6689	likely pathogenic
REVEL	0.186	benign-leaning
SaProt	LLR -6.84	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.7, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 126 kb · p 5.7e-14 · regional, not allelic
Overall
CADD	22.8	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

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,040 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,614,184 alleles · very rare exomes 2/1,461,888 · genomes 0/152,296 · joint denominator

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.Pro357Ser
Coding: c.1069C>T
MANE Select: NM_016169
dbSNP: rs2135930032
Type: single nucleotide variant
Location: chr10:102615314 (GRCh38)
Gene constraint: LOEUF 0.214 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.95 · 10 PDB
Residue 357: the 'disordered' region; a UniProt-annotated variant site (sequence variant)

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 p.Pro357= Likely benign ★★ same residue
SUFU p.Pro357_Ile361del 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

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-pro357ser (accessed [today's date]).

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