Is BSPRY p.Asn339Ser (c.1016A>G) pathogenic?

BSPRY p.Asn339Ser (c.1016A>G) is classified Uncertain significance in BSPRY (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-23). AlphaMissense: likely benign (0.0872); Ultra-rare (popmax 0.0223%, eas).

How common is BSPRY p.Asn339Ser (c.1016A>G) in the general population?

BSPRY p.Asn339Ser (c.1016A>G) is ultra-rare (popmax 0.0223%, eas) (gnomAD).

What do computational predictors say about BSPRY p.Asn339Ser (c.1016A>G)?

AlphaMissense predicts likely benign (score 0.0872) — an in-silico prediction, not a clinical call.

BSPRY p.Asn339Ser

c.1016A>G · VCV3825859

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0872 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0872	likely benign
REVEL	0.065	moderately benign-leaning
SaProt	LLR -5.99	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 2.5	GERP -4.2, phastCons 0.002
Regional constraint	o/e 0.98	unconstrained · MANE · 21 kb · p 0.66 · regional, not allelic
Overall
CADD	5.836	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 0.0223% East Asian · 10/44,880 alleles

Filtering AF 0.012% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00916%

Overall 0.00274% 40/1,461,836 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0223%	4,488
Remaining individualsnot grpmax-eligible	0.0032%	31,253
African / African-American	0.00266%	37,524
European (non-Finnish)	0.00212%	47,201
Finnishnot grpmax-eligible	0.00156%	63,982

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: BSPRY
Protein: p.Asn339Ser
Coding: c.1016A>G
MANE Select: NM_017688
Type: single nucleotide variant
Location: chr9:113369949 (GRCh38)
Gene constraint: LOEUF 1.216 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.75
Residue 339: the b30.2/spry domain

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

Similar variants

BSPRY p.Gly373Ser Uncertain significance ★★ ⚠ same type
BSPRY p.Ala261Pro Uncertain significance ★ ⚠ same type
BSPRY p.Ala287Gly Uncertain significance ★ ⚠ same type
BSPRY p.Ala287Ser Uncertain significance ★ ⚠ same type
BSPRY p.Ala287Val Uncertain significance ★ ⚠ same type
BSPRY p.Ala45Gly Uncertain significance ★ ⚠ same type
BSPRY p.Ala82Val Uncertain significance ★ ⚠ same type
BSPRY p.Arg113Trp 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/bspry-p-asn339ser (accessed [today's date]).

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