Is BIRC6 p.Lys2959= (c.8877A>G) pathogenic?

BIRC6 p.Lys2959= (c.8877A>G) is classified Likely benign in BIRC6 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-29). Rare (popmax 0.553%, eas); Associated with BIRC6-related disorder.

What condition is associated with BIRC6 p.Lys2959= (c.8877A>G)?

BIRC6 p.Lys2959= (c.8877A>G) is associated with BIRC6-related disorder (ClinVar).

How common is BIRC6 p.Lys2959= (c.8877A>G) in the general population?

BIRC6 p.Lys2959= (c.8877A>G) is rare (popmax 0.553%, eas) (gnomAD).

BIRC6 p.Lys2959=

c.8877A>G · rs3731580 · VCV3052652

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.553%, eas)

Conditions

BIRC6-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP -0.065, phastCons 1
Overall
CADD	6.828	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.553% East Asian · 248/44,884 alleles

Filtering AF 0.496% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.474%

Overall 0.0215% 347/1,614,014 alleles · rare exomes 304/1,461,698 · genomes 43/152,316 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.553%	181
Ashkenazi Jewishnot grpmax-eligible	0.0338%	2,961
Remaining individualsnot grpmax-eligible	0.0272%	3,676
South Asian	0.0176%	5,693
European (non-Finnish)	0.00449%	22,262
Admixed American	0.00333%	30,012
Finnishnot grpmax-eligible	0.00156%	64,022

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.Lys2959=
Coding: c.8877A>G
MANE Select: NM_016252
dbSNP: rs3731580
Type: single nucleotide variant
Location: chr2:32499955 (GRCh38)
Gene constraint: LOEUF 0.213 · pLI 1.00 (gnomAD)
Residue 2959: the 'disordered' region

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

Disease context

BIRC6-related disorder

Similar variants

BIRC6 p.Gln853Arg Uncertain significance ★★ ⚠ same condition
BIRC6 p.Glu4506Asp Uncertain significance ★★ ⚠ same condition
BIRC6 p.Arg1075Gln Uncertain significance ★ ⚠ same condition
BIRC6 p.Asp386Glu Uncertain significance ★ same condition
BIRC6 p.Asp673His Uncertain significance ★ same condition
BIRC6 p.Ser1258Ala Uncertain significance ★ ⚠ same condition
BIRC6 p.Ser3427Phe Uncertain significance ★ same condition
BIRC6 p.Asp3819Tyr Uncertain significance same condition

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-lys2959 (accessed [today's date]).

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