Is B9D2 p.Val128Met (c.382G>A) pathogenic?

B9D2 p.Val128Met (c.382G>A) is classified Uncertain significance in B9D2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-07). AlphaMissense: ambiguous (0.3957); Very rare (popmax 0.00534%, afr).

How common is B9D2 p.Val128Met (c.382G>A) in the general population?

B9D2 p.Val128Met (c.382G>A) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about B9D2 p.Val128Met (c.382G>A)?

AlphaMissense predicts ambiguous (score 0.3957) — an in-silico prediction, not a clinical call.

B9D2 p.Val128Met

c.382G>A · VCV3983914

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3957 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Computational evidence

Protein change
AlphaMissense	0.3957	ambiguous
REVEL	0.31	indeterminate
SaProt	LLR -5.35	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.3, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 8,816 bp · p 0.14 · regional, not allelic
Overall
CADD	25.3	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 0.00534% African / African-American · 4/74,930 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00136% 22/1,613,824 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,732
South Asian	0.00439%	22,772
East Asian	0.00223%	44,892
Admixed American	0.00167%	60,008
European (non-Finnish)	0.00102%	98,333

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.Val128Met
Coding: c.382G>A
MANE Select: NM_030578
Type: single nucleotide variant
Location: chr19:41354846 (GRCh38)
Gene constraint: LOEUF 1.518 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.79

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-val128met (accessed [today's date]).

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