Is B9D2 p.Gln83Arg (c.248A>G) pathogenic?

B9D2 p.Gln83Arg (c.248A>G) is classified Uncertain significance in B9D2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-06). AlphaMissense: likely benign (0.2326); Very rare (popmax 0.00134%, afr).

How common is B9D2 p.Gln83Arg (c.248A>G) in the general population?

B9D2 p.Gln83Arg (c.248A>G) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about B9D2 p.Gln83Arg (c.248A>G)?

AlphaMissense predicts likely benign (score 0.2326) — an in-silico prediction, not a clinical call.

B9D2 p.Gln83Arg

c.248A>G · VCV3816551

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2326 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2326	likely benign
REVEL	0.391	indeterminate
SaProt	LLR -7.81	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 7.8	GERP 1.3, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 8,816 bp · p 0.14 · regional, not allelic
Overall
CADD	22.4	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 0.00134% African / African-American · 1/74,860 alleles

Overall 6.87e-05% 1/1,455,310 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.Gln83Arg
Coding: c.248A>G
MANE Select: NM_030578
Type: single nucleotide variant
Location: chr19:41354980 (GRCh38)
Gene constraint: LOEUF 1.518 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.79
Residue 83: the c2 b9-type domain

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

Similar variants

B9D2 p.Gly155Ser Pathogenic/Likely pathogenic ★★ same type
B9D2 p.Pro74Ser Pathogenic/Likely pathogenic ★★ same type
B9D2 p.Ser101Arg Pathogenic/Likely pathogenic ★★ same type
B9D2 p.Ala31Glu Uncertain significance ★★ ⚠ same type
B9D2 p.Arg120Gln Uncertain significance ★★ ⚠ same type
B9D2 p.Arg166Cys Uncertain significance ★★ ⚠ same type
B9D2 p.Arg88Cys Uncertain significance ★★ ⚠ same type
B9D2 p.Gln50His Uncertain significance ★★ ⚠ same type

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-gln83arg (accessed [today's date]).

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