Is B9D2 p.Leu116= (c.346C>T) pathogenic?

B9D2 p.Leu116= (c.346C>T) is classified Likely benign in B9D2 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-03-01). Absent from gnomAD v4.1; Associated with Meckel syndrome.

What condition is associated with B9D2 p.Leu116= (c.346C>T)?

B9D2 p.Leu116= (c.346C>T) is associated with Meckel syndrome, Joubert syndrome (ClinVar).

How common is B9D2 p.Leu116= (c.346C>T) in the general population?

B9D2 p.Leu116= (c.346C>T) is absent from gnomAD v4.1 (gnomAD).

B9D2 p.Leu116=

c.346C>T · rs1555755825 · VCV461770

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Meckel syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP 0.24, phastCons 1
Overall
CADD	8.74	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: B9D2
Protein: p.Leu116=
Coding: c.346C>T
MANE Select: NM_030578
dbSNP: rs1555755825
Type: single nucleotide variant
Location: chr19:41354882 (GRCh38)
Gene constraint: LOEUF 1.518 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.79
Residue 116: the c2 b9-type domain

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

Disease context

Meckel syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Joubert syndrome

Similar variants

B9D2 p.Gly155Ser Pathogenic/Likely pathogenic ★★ same condition
B9D2 p.Pro74Ser Pathogenic/Likely pathogenic ★★ same condition
B9D2 p.Arg88Cys Uncertain significance ★★ ⚠ same condition
B9D2 p.Gln50His Uncertain significance ★★ ⚠ same condition
B9D2 p.Gly162Cys Uncertain significance ★★ ⚠ same condition
B9D2 p.Pro103Ser Uncertain significance ★★ ⚠ same condition
B9D2 p.Thr44Met Uncertain significance ★★ ⚠ same condition
B9D2 p.Val39Met 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/b9d2-p-leu116 (accessed [today's date]).

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