Is B9D2 p.Ala55Asp (c.164C>A) pathogenic?

B9D2 p.Ala55Asp (c.164C>A) is classified Uncertain significance in B9D2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-15). AlphaMissense: likely pathogenic (0.9437); Ultra-rare (popmax 0.0178%, eas).

How common is B9D2 p.Ala55Asp (c.164C>A) in the general population?

B9D2 p.Ala55Asp (c.164C>A) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

What do computational predictors say about B9D2 p.Ala55Asp (c.164C>A)?

AlphaMissense predicts likely pathogenic (score 0.9437) — an in-silico prediction, not a clinical call.

B9D2 p.Ala55Asp

c.164C>A · rs749915355 · VCV3132733

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9437 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9437	likely pathogenic
REVEL	0.751	pathogenic-leaning
SaProt	LLR -13.01	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 8,816 bp · p 0.14 · regional, not allelic
Overall
CADD	28.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0178% East Asian · 8/44,882 alleles

Filtering AF 0.00883% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.00062% 10/1,614,152 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,610
Remaining individualsnot grpmax-eligible	0.0016%	62,506
European (non-Finnish)	8.47e-05%	1,180,018

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.Ala55Asp
Coding: c.164C>A
MANE Select: NM_030578
dbSNP: rs749915355
Type: single nucleotide variant
Location: chr19:41357947 (GRCh38)
Gene constraint: LOEUF 1.518 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.79
Residue 55: the c2 b9-type domain

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

Similar variants

B9D2 p.Ala55Thr Uncertain significance ★ ⚠ same residue
B9D2 p.Ala55Asn Uncertain significance ★ same residue
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

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-ala55asp (accessed [today's date]).

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