Is RBFOX2 p.Thr397= (c.1191C>T) pathogenic?

RBFOX2 p.Thr397= (c.1191C>T) is classified Likely benign in RBFOX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-14). Ultra-rare (popmax 0.0331%, mid); Associated with Inborn genetic diseases.

What condition is associated with RBFOX2 p.Thr397= (c.1191C>T)?

RBFOX2 p.Thr397= (c.1191C>T) is associated with Inborn genetic diseases (ClinVar).

How common is RBFOX2 p.Thr397= (c.1191C>T) in the general population?

RBFOX2 p.Thr397= (c.1191C>T) is ultra-rare (popmax 0.0331%, mid) (gnomAD).

RBFOX2 p.Thr397=

c.1191C>T · VCV4151396

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0331%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.039	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.3	GERP -4.8
Overall
CADD	9.967	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0331% Middle Eastern · 2/6,048 alleles

Filtering AF 0.00583% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.00168% 27/1,609,748 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0331%	3,024
Remaining individualsnot grpmax-eligible	0.00963%	10,385
African / African-American	0.00802%	12,466
East Asian	0.00448%	22,304
South Asian	0.0011%	90,620
European (non-Finnish)	0.000849%	117,772

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: RBFOX2
Protein: p.Thr397=
Coding: c.1191C>T
MANE Select: NM_001349999
Type: single nucleotide variant
Location: chr22:35746508 (GRCh38)
Gene constraint: LOEUF 0.336 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 55.86 · 1 PDB

Full RBFOX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RBFOX2 p.Asp417Asn Uncertain significance ★★ same condition
RBFOX2 p.Glu229Gln Uncertain significance ★★ same condition
RBFOX2 p.Gly133Arg Uncertain significance ★★ same condition
RBFOX2 p.Gly409Ser Uncertain significance ★★ same condition
RBFOX2 p.Met91Val Uncertain significance ★★ same condition
RBFOX2 p.Pro104Leu Uncertain significance ★★ same condition
RBFOX2 p.Pro307Ser Uncertain significance ★★ same condition
RBFOX2 p.Ala401= Likely 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/rbfox2-p-thr397 (accessed [today's date]).

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