Is B9D2 p.Arg170Cys (c.508C>T) pathogenic?

B9D2 p.Arg170Cys (c.508C>T) is classified Uncertain significance in B9D2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-15). AlphaMissense: likely benign (0.2056); Very rare (popmax 0.00686%, nfe); Associated with Joubert syndrome.

What condition is associated with B9D2 p.Arg170Cys (c.508C>T)?

B9D2 p.Arg170Cys (c.508C>T) is associated with Joubert syndrome, Meckel syndrome (ClinVar).

How common is B9D2 p.Arg170Cys (c.508C>T) in the general population?

B9D2 p.Arg170Cys (c.508C>T) is very rare (popmax 0.00686%, nfe) (gnomAD).

What do computational predictors say about B9D2 p.Arg170Cys (c.508C>T)?

AlphaMissense predicts likely benign (score 0.2056) — an in-silico prediction, not a clinical call.

B9D2 p.Arg170Cys

c.508C>T · rs371315485 · VCV2102527

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2056 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00686%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Joubert syndrome

Computational evidence

Protein change
AlphaMissense	0.2056	likely benign
REVEL	0.356	indeterminate
SaProt	LLR -11.15	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 1.3, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 8,816 bp · p 0.14 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00686% European (non-Finnish) · 81/1,180,016 alleles

Filtering AF 0.00563% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.00551% 89/1,613,892 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00686%	14,568
Remaining individualsnot grpmax-eligible	0.0048%	20,828
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
African / African-American	0.00267%	37,462
East Asian	0.00223%	44,896
South Asian	0.0011%	91,088

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.Arg170Cys
Coding: c.508C>T
MANE Select: NM_030578
dbSNP: rs371315485
Type: single nucleotide variant
Location: chr19:41354720 (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.Arg170Gly Uncertain significance ★ ⚠ same residue
B9D2 p.Arg170His 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

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-arg170cys (accessed [today's date]).

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