Is B9D2 p.Arg75fs (c.223_224insT) pathogenic?

B9D2 p.Arg75fs (c.223224insT) is classified Likely pathogenic in B9D2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-30). Absent from gnomAD; Associated with Joubert syndrome and related disorders.

What condition is associated with B9D2 p.Arg75fs (c.223_224insT)?

B9D2 p.Arg75fs (c.223_224insT) is associated with Joubert syndrome and related disorders (ClinVar).

How common is B9D2 p.Arg75fs (c.223_224insT) in the general population?

B9D2 p.Arg75fs (c.223_224insT) is absent from gnomAD (gnomAD).

B9D2 p.Arg75fs

c.223_224insT · rs2513398193 · VCV2501262

Likely pathogenic Single submitter

Classification

Likely 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

Joubert syndrome and related disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (4 of 4) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.8	GERP 0.27, 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: B9D2
Protein: p.Arg75fs
Coding: c.223_224insT
MANE Select: NM_030578
dbSNP: rs2513398193
Type: Insertion
Location: chr19:41355004 (GRCh38)
Gene constraint: LOEUF 1.518 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.79
Residue 75: the c2 b9-type domain

Full B9D2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Joubert syndrome and related disorders — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

B9D2 p.Arg75Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
B9D2 p.Arg75Gly Uncertain significance ★ ⚠ same residue
B9D2 p.Gly155Ser Pathogenic/Likely pathogenic ★★ same condition
B9D2 p.Pro74Ser Pathogenic/Likely pathogenic ★★ same condition
B9D2 p.Ser101Arg Pathogenic/Likely pathogenic ★★ ⚠ same condition
B9D2 p.Ala13fs Likely pathogenic ★ same condition
B9D2 c.-4-60_-4-59insT Benign ★★ same type

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/b9d2-p-arg75fs (accessed [today's date]).

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