Is FGF13 p.Ser46Phe (c.137C>T) pathogenic?

FGF13 p.Ser46Phe (c.137C>T) is classified Uncertain significance in FGF13 (ClinVar, Single submitter, 2 submitters; last evaluated 2022-10-29). Very rare (popmax 0.000784%, nfe); Associated with developmental and epileptic encephalopathy, 90.

What condition is associated with FGF13 p.Ser46Phe (c.137C>T)?

FGF13 p.Ser46Phe (c.137C>T) is associated with developmental and epileptic encephalopathy, 90 (ClinVar).

How common is FGF13 p.Ser46Phe (c.137C>T) in the general population?

FGF13 p.Ser46Phe (c.137C>T) is very rare (popmax 0.000784%, nfe) (gnomAD).

FGF13 p.Ser46Phe

c.137C>T · rs756270099 · VCV2441792

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000784%, nfe)

Conditions

developmental and epileptic encephalopathy, 90

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.406	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Overall
CADD	25.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000784% European (non-Finnish) · 7/892,707 alleles

Filtering AF 0.000326% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00021%

Overall 0.00058% 7/1,207,314 alleles · very rare exomes 7/1,093,692 · genomes 0/113,622 · 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: FGF13
Protein: p.Ser46Phe
Coding: c.137C>T
MANE Select: NM_004114 · reported on NM_001139500
dbSNP: rs756270099
Type: single nucleotide variant
Location: chrX:138857592 (GRCh38)
Structure: AlphaFold pLDDT 80.27 · 3 PDB
Residue 46: the 'mediates targeting to the nucleus' region

Full FGF13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

developmental and epileptic encephalopathy, 90 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FGF13 p.Arg11Cys Pathogenic ★★ same condition
FGF13 p.Ser97Gly Uncertain significance ★★ ⚠ same condition
FGF13 p.Arg14Thr Pathogenic ★ same condition
FGF13 p.Ile5Ser Likely pathogenic ★ ⚠ same condition
FGF13 p.Ser8Ter Pathogenic ★ same condition
FGF13 c.403-1G>A Uncertain significance ★ same condition
FGF13 p.Ala39Val Uncertain significance ★ same condition
FGF13 p.Arg161His 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/fgf13-p-ser46phe (accessed [today's date]).

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