Is FGF14 p.Pro87= (c.261C>T) pathogenic?

FGF14 p.Pro87= (c.261C>T) is classified Benign/Likely benign in FGF14 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-07). Ultra-rare (popmax 0.0959%, eas); Associated with spinocerebellar ataxia type 27.

What condition is associated with FGF14 p.Pro87= (c.261C>T)?

FGF14 p.Pro87= (c.261C>T) is associated with spinocerebellar ataxia type 27 (ClinVar).

How common is FGF14 p.Pro87= (c.261C>T) in the general population?

FGF14 p.Pro87= (c.261C>T) is ultra-rare (popmax 0.0959%, eas) (gnomAD).

How is Spinocerebellar ataxia type 27A inherited?

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

FGF14 p.Pro87=

c.261C>T · rs757210660 · VCV882586

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0959%, eas)

Conditions

spinocerebellar ataxia type 27

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 -2.2	GERP -2.5
Overall
CADD	9.402	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0959% East Asian · 43/44,848 alleles

Filtering AF 0.0731% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0651%

Overall 0.00459% 74/1,613,416 alleles · ultra-rare exomes 65/1,461,232 · genomes 9/152,184 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0959%	1,043
South Asian	0.0176%	5,692
Middle Eastern	0.0165%	6,056
Remaining individualsnot grpmax-eligible	0.0064%	15,617
Finnishnot grpmax-eligible	0.00156%	64,010
European (non-Finnish)	0.000763%	131,058

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: FGF14
Protein: p.Pro87=
Coding: c.261C>T
MANE Select: NM_004115
dbSNP: rs757210660
Type: single nucleotide variant
Location: chr13:101875229 (GRCh38)
Gene constraint: LOEUF 0.482 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 79.77

Full FGF14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

spinocerebellar ataxia type 27 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Spinocerebellar ataxia type 27A (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult

Similar variants

FGF14 p.Pro87Leu Uncertain significance ★★ ⚠ same residue
FGF14 p.Pro87Thr Uncertain significance ★ ⚠ same residue
FGF14 c.408+1G>A Likely pathogenic ★★ same condition
FGF14 p.Arg207Gln Uncertain significance ★★ ⚠ same condition
FGF14 p.Pro24Leu Uncertain significance ★★ ⚠ same condition
FGF14 c.608-10C>T Benign ★★ same condition
FGF14 c.*1259C>T Benign/Likely benign ★★ same condition
FGF14 c.*1612G>T Benign ★★ 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/fgf14-p-pro87 (accessed [today's date]).

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