Is BIRC6 p.Arg3286Gln (c.9857G>A) pathogenic?

BIRC6 p.Arg3286Gln (c.9857G>A) is classified Uncertain significance in BIRC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-03). AlphaMissense: ambiguous (0.3894); Ultra-rare (popmax 0.012%, nfe).

How common is BIRC6 p.Arg3286Gln (c.9857G>A) in the general population?

BIRC6 p.Arg3286Gln (c.9857G>A) is ultra-rare (popmax 0.012%, nfe) (gnomAD).

What do computational predictors say about BIRC6 p.Arg3286Gln (c.9857G>A)?

AlphaMissense predicts ambiguous (score 0.3894) — an in-silico prediction, not a clinical call.

BIRC6 p.Arg3286Gln

c.9857G>A · rs760929182 · VCV2361392

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3894 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3894	ambiguous
REVEL	0.761	pathogenic-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 1,745 bp · p 1.2e-05 · regional, not allelic
Overall
CADD	25.6	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 0.012% European (non-Finnish) · 142/1,179,884 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0098%

Overall 0.00923% 149/1,613,714 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.012%	8,309
Remaining individualsnot grpmax-eligible	0.0064%	15,615
African / African-American	0.00401%	24,943

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: BIRC6
Protein: p.Arg3286Gln
Coding: c.9857G>A
MANE Select: NM_016252
dbSNP: rs760929182
Type: single nucleotide variant
Location: chr2:32508136 (GRCh38)
Gene constraint: LOEUF 0.213 · pLI 1.00 (gnomAD)

Full BIRC6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BIRC6 p.Arg3286Trp Uncertain significance ★ ⚠ same residue
BIRC6 p.Gln853Arg Uncertain significance ★★ ⚠ same type
BIRC6 p.Glu4506Asp Uncertain significance ★★ ⚠ same type
BIRC6 c.7409-6T>C Likely benign ★★ same type
BIRC6 p.Ala1549= Benign ★★ same type
BIRC6 p.Ala3622Val Likely benign ★★ same type
BIRC6 p.Ala4466= Benign/Likely benign ★★ same type
BIRC6 p.Arg4605= Benign ★★ 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/birc6-p-arg3286gln (accessed [today's date]).

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