Is BIN3 p.Asn69Ser (c.206A>G) pathogenic?

BIN3 p.Asn69Ser (c.206A>G) is classified Uncertain significance in BIN3 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-02-07). AlphaMissense: likely benign (0.1208); Ultra-rare (popmax 0.0936%, eas).

How common is BIN3 p.Asn69Ser (c.206A>G) in the general population?

BIN3 p.Asn69Ser (c.206A>G) is ultra-rare (popmax 0.0936%, eas) (gnomAD).

What do computational predictors say about BIN3 p.Asn69Ser (c.206A>G)?

AlphaMissense predicts likely benign (score 0.1208) — an in-silico prediction, not a clinical call.

BIN3 p.Asn69Ser

c.206A>G · rs368195300 · VCV2462212

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1208 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0936%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1208	likely benign
REVEL	0.135	moderately benign-leaning
SaProt	LLR -5.16	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 6.1	GERP 1.6, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 48 kb · p 0.041 · regional, not allelic
Overall
CADD	21.5	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 0.0936% East Asian · 42/44,878 alleles

Filtering AF 0.0712% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0632%

Overall 0.0123% 199/1,613,976 alleles · ultra-rare exomes 180/1,461,696 · genomes 19/152,280 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0936%	1,069
Middle Eastern	0.066%	1,516
South Asian	0.0307%	3,253
Admixed American	0.03%	3,335
Remaining individualsnot grpmax-eligible	0.0128%	7,811
Finnishnot grpmax-eligible	0.0109%	9,146
African / African-American	0.008%	12,504
European (non-Finnish)	0.00729%	13,720

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: BIN3
Protein: p.Asn69Ser
Coding: c.206A>G
MANE Select: NM_018688
dbSNP: rs368195300
Type: single nucleotide variant
Location: chr8:22630533 (GRCh38)
Gene constraint: LOEUF 1.45 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.83
Residue 69: the bar domain

Full BIN3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BIN3 c.297+5C>T Benign ★★ same type
BIN3 p.Ala131Pro Uncertain significance ★ ⚠ same type
BIN3 p.Arg128Gln Uncertain significance ★ ⚠ same type
BIN3 p.Arg128Trp Uncertain significance ★ ⚠ same type
BIN3 p.Arg136Gly Uncertain significance ★ ⚠ same type
BIN3 p.Arg166Gln Uncertain significance ★ ⚠ same type
BIN3 p.Arg185Cys Uncertain significance ★ ⚠ same type
BIN3 p.Arg203Gln 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/bin3-p-asn69ser (accessed [today's date]).

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