Is B9D2 p.Ser101Arg (c.301A>C) pathogenic?

B9D2 p.Ser101Arg (c.301A>C) is classified Pathogenic/Likely pathogenic in B9D2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-08-10). AlphaMissense: likely pathogenic (0.9784); Very rare (popmax 0.00989%, sas); Associated with B9D2-related disorders.

What condition is associated with B9D2 p.Ser101Arg (c.301A>C)?

B9D2 p.Ser101Arg (c.301A>C) is associated with B9D2-related disorders, Meckel syndrome, type 10, Joubert syndrome and related disorders (ClinVar).

How common is B9D2 p.Ser101Arg (c.301A>C) in the general population?

B9D2 p.Ser101Arg (c.301A>C) is very rare (popmax 0.00989%, sas) (gnomAD).

What do computational predictors say about B9D2 p.Ser101Arg (c.301A>C)?

AlphaMissense predicts likely pathogenic (score 0.9784) — an in-silico prediction, not a clinical call.

B9D2 p.Ser101Arg

c.301A>C · rs1487082103 · VCV30931

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9784 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00989%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

B9D2-related disorders

Computational evidence

Protein change
AlphaMissense	0.9784	likely pathogenic ✓ concordant with ClinVar · top 7% in B9D2
REVEL	0.368	indeterminate
SaProt	LLR -9.83	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.1, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 8,816 bp · p 0.14 · regional, not allelic
Overall
CADD	26.4	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 0.00989% South Asian · 9/91,006 alleles

Filtering AF 0.00514% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00376%

Overall 0.000616% 9/1,460,984 alleles · very 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.Ser101Arg
Coding: c.301A>C
MANE Select: NM_030578
dbSNP: rs1487082103
Type: single nucleotide variant
Location: chr19:41354927 (GRCh38)
Gene constraint: LOEUF 1.518 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.79
Residue 101: the c2 b9-type domain; a UniProt-annotated variant site (in mks10; loss-of-function; could not rescue in vitro dosage-dependent ciliary defects; fails to interact with mks1 although it retains its ability to interact with b9d1)

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

Disease context

B9D2-related disorders

Also linked: Meckel syndrome, type 10 Joubert syndrome and related disorders

Similar variants

B9D2 p.Gly155Ser Pathogenic/Likely pathogenic ★★ same condition
B9D2 p.Pro74Ser Pathogenic/Likely pathogenic ★★ same condition
B9D2 p.Arg166Cys Uncertain significance ★★ ⚠ same condition
B9D2 p.Gly162Cys Uncertain significance ★★ ⚠ same condition
B9D2 p.Pro103Ser Uncertain significance ★★ ⚠ same condition
B9D2 c.214+25T>G Benign ★★ same condition
B9D2 c.88+6C>T Benign/Likely benign ★★ same condition
B9D2 c.-4-40C>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-ser101arg (accessed [today's date]).

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