Is B9D2 p.Ser85Asn (c.254G>A) pathogenic?

B9D2 p.Ser85Asn (c.254G>A) is classified Uncertain significance in B9D2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-01). AlphaMissense: likely benign (0.1161); Ultra-rare (popmax 0.0661%, mid).

How common is B9D2 p.Ser85Asn (c.254G>A) in the general population?

B9D2 p.Ser85Asn (c.254G>A) is ultra-rare (popmax 0.0661%, mid) (gnomAD).

What do computational predictors say about B9D2 p.Ser85Asn (c.254G>A)?

AlphaMissense predicts likely benign (score 0.1161) — an in-silico prediction, not a clinical call.

B9D2 p.Ser85Asn

c.254G>A · VCV3473882

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1161 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0661%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1161	likely benign
REVEL	0.104	moderately benign-leaning
SaProt	LLR -8.60	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.6	GERP 1.3, phastCons 0.98
Regional constraint	o/e 0.90	unconstrained · MANE · 8,816 bp · p 0.14 · regional, not allelic
Overall
CADD	18.5	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 0.0661% Middle Eastern · 4/6,048 alleles

Filtering AF 0.0226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.00186% 30/1,610,282 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0661%	1,512
South Asian	0.00882%	11,337
Remaining individualsnot grpmax-eligible	0.00802%	12,464
European (non-Finnish)	0.0011%	90,623

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.Ser85Asn
Coding: c.254G>A
MANE Select: NM_030578
Type: single nucleotide variant
Location: chr19:41354974 (GRCh38)
Gene constraint: LOEUF 1.518 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.79
Residue 85: 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-ser85asn (accessed [today's date]).

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