Is BIRC6 p.Thr2017= (c.6051A>G) pathogenic?

BIRC6 p.Thr2017= (c.6051A>G) is classified Likely benign in BIRC6 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-13). Ultra-rare (popmax 0.0281%, nfe); Associated with BIRC6-related disorder.

What condition is associated with BIRC6 p.Thr2017= (c.6051A>G)?

BIRC6 p.Thr2017= (c.6051A>G) is associated with BIRC6-related disorder (ClinVar).

How common is BIRC6 p.Thr2017= (c.6051A>G) in the general population?

BIRC6 p.Thr2017= (c.6051A>G) is ultra-rare (popmax 0.0281%, nfe) (gnomAD).

BIRC6 p.Thr2017=

c.6051A>G · rs149167251 · VCV3041249

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0281%, nfe)

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 -4.1	GERP -5.6
Overall
CADD	0.302	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0281% European (non-Finnish) · 332/1,179,848 alleles

Filtering AF 0.0256% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0246%

Overall 0.0223% 360/1,613,980 alleles · ultra-rare exomes 327/1,461,648 · genomes 33/152,332 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0281%	3,554
Remaining individualsnot grpmax-eligible	0.0256%	3,906
African / African-American	0.00933%	10,723
Admixed American	0.00666%	15,006
Finnishnot grpmax-eligible	0.00156%	64,016

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.Thr2017=
Coding: c.6051A>G
MANE Select: NM_016252
dbSNP: rs149167251
Type: single nucleotide variant
Location: chr2:32468707 (GRCh38)
Gene constraint: LOEUF 0.213 · pLI 1.00 (gnomAD)
Residue 2017: an α-helix

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-thr2017 (accessed [today's date]).

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