Is B9D1 p.Pro199= (c.597C>G) pathogenic?

B9D1 p.Pro199= (c.597C>G) is classified Conflicting classifications of pathogenicity in B9D1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-22). Rare (popmax 0.15%, amr); Associated with Meckel syndrome.

What condition is associated with B9D1 p.Pro199= (c.597C>G)?

B9D1 p.Pro199= (c.597C>G) is associated with Meckel syndrome, Meckel syndrome, type 9, Joubert syndrome (ClinVar).

How common is B9D1 p.Pro199= (c.597C>G) in the general population?

B9D1 p.Pro199= (c.597C>G) is rare (popmax 0.15%, amr) (gnomAD).

B9D1 p.Pro199=

c.597C>G · rs753785719 · VCV388102

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.15%, amr)

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 -0.84	GERP -3.5
Overall
CADD	0.42	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.15% Admixed American · 90/60,008 alleles

Filtering AF 0.125% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.116%

Overall 0.0075% 121/1,614,052 alleles · rare exomes 110/1,461,844 · genomes 11/152,208 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.15%	667
Middle Eastern	0.0329%	3,037
Remaining individualsnot grpmax-eligible	0.0144%	6,943
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,869
African / African-American	0.004%	24,973
European (non-Finnish)	0.00119%	84,287

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: B9D1
Protein: p.Pro199=
Coding: c.597C>G
MANE Select: NM_015681
dbSNP: rs753785719
Type: single nucleotide variant
Location: chr17:19343337 (GRCh38)
Gene constraint: LOEUF 1.023 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.05
Residue 199: the 'disordered' region

Full B9D1 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: Meckel syndrome, type 9 Joubert syndrome

Similar variants

B9D1 c.341+2T>C Pathogenic/Likely pathogenic ★★ same condition
B9D1 p.Arg114Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
B9D1 p.Arg156Trp Pathogenic/Likely pathogenic ★★ same condition
B9D1 c.404+5G>C Uncertain significance ★★ same condition
B9D1 p.Ala44Val Uncertain significance ★★ ⚠ same condition
B9D1 p.Arg101Gln Uncertain significance ★★ same condition
B9D1 p.Arg140Gln Uncertain significance ★★ ⚠ same condition
B9D1 p.Arg162His 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/b9d1-p-pro199 (accessed [today's date]).

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