Is FAT2 p.Ser3299Phe (c.9896C>T) pathogenic?

FAT2 p.Ser3299Phe (c.9896C>T) is classified Uncertain significance in FAT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-12). AlphaMissense: likely benign (0.1158); Absent from gnomAD v4.1; Associated with spinocerebellar ataxia 45.

What condition is associated with FAT2 p.Ser3299Phe (c.9896C>T)?

FAT2 p.Ser3299Phe (c.9896C>T) is associated with spinocerebellar ataxia 45 (ClinVar).

How common is FAT2 p.Ser3299Phe (c.9896C>T) in the general population?

FAT2 p.Ser3299Phe (c.9896C>T) is absent from gnomAD v4.1 (gnomAD).

How is Spinocerebellar ataxia type 45 inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about FAT2 p.Ser3299Phe (c.9896C>T)?

AlphaMissense predicts likely benign (score 0.1158) — an in-silico prediction, not a clinical call.

FAT2 p.Ser3299Phe

c.9896C>T · rs2127588750 · VCV1180502

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1158 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

spinocerebellar ataxia 45

Computational evidence

Protein change
AlphaMissense	0.1158	likely benign
REVEL	0.234	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 28 kb · p 2.4e-06 · regional, not allelic
Overall
CADD	26.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

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: FAT2
Protein: p.Ser3299Phe
Coding: c.9896C>T
MANE Select: NM_001447
dbSNP: rs2127588750
Type: single nucleotide variant
Location: chr5:151529308 (GRCh38)
Gene constraint: LOEUF 0.554 · pLI <0.01 (gnomAD)
Residue 3299: the cadherin 29 domain

Full FAT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

spinocerebellar ataxia 45 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Spinocerebellar ataxia type 45 (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

FAT2 p.Ala1079Asp Uncertain significance ★★ ⚠ same condition
FAT2 p.Arg3558Gln Uncertain significance ★★ ⚠ same condition
FAT2 p.Gly1261Arg Uncertain significance ★★ ⚠ same condition
FAT2 p.Leu3279Val Uncertain significance ★★ ⚠ same condition
FAT2 p.Lys2586Arg Uncertain significance ★★ ⚠ same condition
FAT2 p.Pro146Ser Uncertain significance ★★ ⚠ same condition
FAT2 p.Pro1817Ser Uncertain significance ★★ ⚠ same condition
FAT2 p.Thr3931Met 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/fat2-p-ser3299phe (accessed [today's date]).

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