Is B9D2 p.Gly172= (c.516C>T) pathogenic?

B9D2 p.Gly172= (c.516C>T) is classified Likely benign in B9D2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-22). Very rare (popmax 0.00668%, eas); Associated with Joubert syndrome.

What condition is associated with B9D2 p.Gly172= (c.516C>T)?

B9D2 p.Gly172= (c.516C>T) is associated with Joubert syndrome, Meckel syndrome (ClinVar).

How common is B9D2 p.Gly172= (c.516C>T) in the general population?

B9D2 p.Gly172= (c.516C>T) is very rare (popmax 0.00668%, eas) (gnomAD).

B9D2 p.Gly172=

c.516C>T · rs141578342 · VCV2934918

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Conditions

Joubert 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 -9	GERP -2.6
Overall
CADD	0.44	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% East Asian · 3/44,898 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00198% 32/1,613,888 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,966
African / African-American	0.00534%	18,734
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
European (non-Finnish)	0.00186%	53,637
Admixed American	0.00167%	60,002
Remaining individualsnot grpmax-eligible	0.0016%	62,482

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: B9D2
Protein: p.Gly172=
Coding: c.516C>T
MANE Select: NM_030578
dbSNP: rs141578342
Type: single nucleotide variant
Location: chr19:41354712 (GRCh38)
Gene constraint: LOEUF 1.518 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.79

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

Disease context

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

Also linked: Meckel syndrome

Similar variants

B9D2 p.Gly172Ser Uncertain significance ★ ⚠ same residue
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

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-gly172 (accessed [today's date]).

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