Is B9D2 p.Gln50His (c.150G>C) pathogenic?

B9D2 p.Gln50His (c.150G>C) is classified Uncertain significance in B9D2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-30). AlphaMissense: likely benign (0.2745); Ultra-rare (popmax 0.0583%, amr); Associated with Meckel syndrome.

What condition is associated with B9D2 p.Gln50His (c.150G>C)?

B9D2 p.Gln50His (c.150G>C) is associated with Meckel syndrome, Joubert syndrome (ClinVar).

How common is B9D2 p.Gln50His (c.150G>C) in the general population?

B9D2 p.Gln50His (c.150G>C) is ultra-rare (popmax 0.0583%, amr) (gnomAD).

What do computational predictors say about B9D2 p.Gln50His (c.150G>C)?

AlphaMissense predicts likely benign (score 0.2745) — an in-silico prediction, not a clinical call.

B9D2 p.Gln50His

c.150G>C · rs747988749 · VCV461768

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2745 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0583%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Meckel syndrome

Computational evidence

Protein change
AlphaMissense	0.2745	likely benign
REVEL	0.45	indeterminate
SaProt	LLR -7.04	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.27	GERP -1.7, phastCons 0.016
Regional constraint	o/e 0.90	unconstrained · MANE · 8,816 bp · p 0.14 · regional, not allelic
Overall
CADD	18.19	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0583% Admixed American · 35/60,020 alleles

Filtering AF 0.0431% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0378%

Overall 0.00239% 35/1,461,862 alleles · ultra-rare

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.Gln50His
Coding: c.150G>C
MANE Select: NM_030578
dbSNP: rs747988749
Type: single nucleotide variant
Location: chr19:41357961 (GRCh38)
Gene constraint: LOEUF 1.518 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.79
Residue 50: 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.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
B9D2 c.215-16C>G 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/b9d2-p-gln50his (accessed [today's date]).

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