Is SUFU p.Phe245Val (c.733T>G) pathogenic?

SUFU p.Phe245Val (c.733T>G) is classified Uncertain significance in SUFU (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-06). AlphaMissense: likely pathogenic (0.9777); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with SUFU p.Phe245Val (c.733T>G)?

SUFU p.Phe245Val (c.733T>G) is associated with hereditary neoplastic syndrome (ClinVar).

How common is SUFU p.Phe245Val (c.733T>G) in the general population?

SUFU p.Phe245Val (c.733T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SUFU p.Phe245Val (c.733T>G)?

AlphaMissense predicts likely pathogenic (score 0.9777) — an in-silico prediction, not a clinical call.

SUFU p.Phe245Val

c.733T>G · rs1337281398 · VCV2562342

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9777 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.9777	likely pathogenic
REVEL	0.93	moderately pathogenic-leaning
SaProt	LLR -9.94	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.8, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 126 kb · p 5.7e-14 · regional, not allelic
Overall
CADD	27.1	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.Phe245Val
Coding: c.733T>G
MANE Select: NM_016169
dbSNP: rs1337281398
Type: single nucleotide variant
Location: chr10:102594042 (GRCh38)
Gene constraint: LOEUF 0.214 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.95 · 10 PDB
Residue 245: 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

Similar variants

SUFU p.Phe245Cys Uncertain significance ★★ ⚠ same residue
SUFU p.Phe245Ser Uncertain significance ★★ ⚠ same residue
SUFU c.1022+1G>A Pathogenic ★★ same condition
SUFU p.Arg146Ter Pathogenic ★★ same condition
SUFU p.Arg299Ter Pathogenic ★★ same condition
SUFU p.Trp88Ter Pathogenic/Likely pathogenic ★★ same condition
SUFU c.1158-3C>T Uncertain significance ★★ same condition
SUFU c.1296+3G>A Uncertain significance ★★ 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-phe245val (accessed [today's date]).

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