Is B9D1 p.Pro120= (c.360C>T) pathogenic?

B9D1 p.Pro120= (c.360C>T) is classified Likely benign in B9D1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-28). Ultra-rare (popmax 0.0853%, afr); Associated with Meckel syndrome.

What condition is associated with B9D1 p.Pro120= (c.360C>T)?

B9D1 p.Pro120= (c.360C>T) is associated with Meckel syndrome, Joubert syndrome (ClinVar).

How common is B9D1 p.Pro120= (c.360C>T) in the general population?

B9D1 p.Pro120= (c.360C>T) is ultra-rare (popmax 0.0853%, afr) (gnomAD).

B9D1 p.Pro120=

c.360C>T · rs139682891 · VCV1115097

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0853%, afr)

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 2.1	GERP -0.38, phastCons 1
Overall
CADD	12.69	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0853% African / African-American · 64/75,046 alleles

Filtering AF 0.0685% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0624%

Overall 0.00471% 76/1,614,226 alleles · ultra-rare exomes 37/1,461,880 · genomes 39/152,346 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0853%	1,173
South Asian	0.00988%	10,121
Admixed American	0.00333%	30,015
European (non-Finnish)	8.47e-05%	1,180,048

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.Pro120=
Coding: c.360C>T
MANE Select: NM_015681
dbSNP: rs139682891
Type: single nucleotide variant
Location: chr17:19347313 (GRCh38)
Gene constraint: LOEUF 1.023 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.05
Residue 120: the c2 b9-type domain

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: Joubert syndrome

Similar variants

B9D1 p.Pro120Ala Uncertain significance ★ ⚠ same residue
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

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-pro120 (accessed [today's date]).

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