Is RBFOX3 p.Ala68= (c.204C>T) pathogenic?

RBFOX3 p.Ala68= (c.204C>T) is classified Likely benign in RBFOX3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-16). Very rare (popmax 0.00429%, sas); Associated with idiopathic generalized epilepsy.

What condition is associated with RBFOX3 p.Ala68= (c.204C>T)?

RBFOX3 p.Ala68= (c.204C>T) is associated with idiopathic generalized epilepsy (ClinVar).

How common is RBFOX3 p.Ala68= (c.204C>T) in the general population?

RBFOX3 p.Ala68= (c.204C>T) is very rare (popmax 0.00429%, sas) (gnomAD).

RBFOX3 p.Ala68=

c.204C>T · rs998084414 · VCV1620286

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00429%, sas)

Conditions

idiopathic generalized epilepsy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -7.8	GERP -4.7
Overall
CADD	2.983	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00429% South Asian · 2/46,640 alleles

Filtering AF 0.00253% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00224%

Overall 0.00352% 47/1,336,120 alleles · very rare exomes 42/1,183,968 · genomes 5/152,152 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0119%	8,415
South Asiangrpmax	0.00429%	23,320
European (non-Finnish)	0.00345%	28,954
African / African-American	0.00306%	32,720
East Asian	0.00305%	32,768

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: RBFOX3
Protein: p.Ala68=
Coding: c.204C>T
MANE Select: NM_001350451
dbSNP: rs998084414
Type: single nucleotide variant
Location: chr17:79115512 (GRCh38)
Gene constraint: LOEUF 0.605 · pLI 0.60 (gnomAD)
Structure: AlphaFold pLDDT 62.27
Residue 68: the 'disordered' region

Full RBFOX3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

idiopathic generalized epilepsy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RBFOX3 p.Ala68Thr Uncertain significance ★★ ⚠ same residue
RBFOX3 p.Ala316Thr Uncertain significance ★★ ⚠ same condition
RBFOX3 p.Ala62Val Uncertain significance ★★ ⚠ same condition
RBFOX3 p.Ala79Val Uncertain significance ★★ ⚠ same condition
RBFOX3 p.Ala8Thr Uncertain significance ★★ ⚠ same condition
RBFOX3 p.Arg230Trp Uncertain significance ★★ ⚠ same condition
RBFOX3 p.Gln31Arg Uncertain significance ★★ ⚠ same condition
RBFOX3 p.Glu61Lys 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/rbfox3-p-ala68 (accessed [today's date]).

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