Is RBFOX2 p.Ser175fs (c.523dup) pathogenic?

RBFOX2 p.Ser175fs (c.523dup) is classified Pathogenic in RBFOX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-06-05). Absent from gnomAD; Associated with Inborn genetic diseases.

What condition is associated with RBFOX2 p.Ser175fs (c.523dup)?

RBFOX2 p.Ser175fs (c.523dup) is associated with Inborn genetic diseases (ClinVar).

How common is RBFOX2 p.Ser175fs (c.523dup) in the general population?

RBFOX2 p.Ser175fs (c.523dup) is absent from gnomAD (gnomAD).

RBFOX2 p.Ser175fs

c.523dup · rs1555902810 · VCV521760

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.7, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: RBFOX2
Protein: p.Ser175fs
Coding: c.523dup
MANE Select: NM_001349999
dbSNP: rs1555902810
Type: Duplication
Location: chr22:35781685 (GRCh38)
Gene constraint: LOEUF 0.336 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 55.86 · 1 PDB
Residue 175: the rrm domain; an α-helix

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-ser175fs (accessed [today's date]).

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