Is FAT2 p.Ser4169= (c.12507C>T) pathogenic?

FAT2 p.Ser4169= (c.12507C>T) is classified Benign in FAT2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-03). Common (popmax 98.5%, eas) — too common for a highly-penetrant pathogenic allele; Associated with spinocerebellar ataxia 45.

What condition is associated with FAT2 p.Ser4169= (c.12507C>T)?

FAT2 p.Ser4169= (c.12507C>T) is associated with spinocerebellar ataxia 45 (ClinVar).

How is Spinocerebellar ataxia type 45 inherited?

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

FAT2 p.Ser4169=

Q: How common is FAT2 p.Ser4169= (c.12507C>T) in the general population?

FAT2 p.Ser4169= (c.12507C>T) is common (popmax 98.5%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.12507C>T · rs7723266 · VCV1220679

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 98.5%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

spinocerebellar ataxia 45

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 -1.1	GERP -3.7
Overall
CADD	0.258	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 98.5% East Asian · 43,953/44,606 alleles

Filtering AF 97.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 97.4%

Overall 82.8% 1,310,689/1,582,430 alleles · common exomes 1,179,408/1,430,216 · genomes 131,281/152,214 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	98.5%	1
African / African-American	94.5%	1
Amishnot grpmax-eligible	92.9%	1
Admixed American	90.3%	1
South Asian	90%	1
Middle Eastern	89.2%	1
Ashkenazi Jewishnot grpmax-eligible	88.2%	1
Remaining individualsnot grpmax-eligible	84.3%	1
Finnishnot grpmax-eligible	80.8%	1
European (non-Finnish)	80.4%	1

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: FAT2
Protein: p.Ser4169=
Coding: c.12507C>T
MANE Select: NM_001447
dbSNP: rs7723266
Type: single nucleotide variant
Location: chr5:151507164 (GRCh38)
Gene constraint: LOEUF 0.554 · pLI <0.01 (gnomAD)

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-ser4169 (accessed [today's date]).

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