Is BIRC6 p.Thr4064= (c.12192C>T) pathogenic?

BIRC6 p.Thr4064= (c.12192C>T) is classified Benign in BIRC6 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-28). Low-frequency (popmax 1.49%, afr); Associated with BIRC6-related disorder.

What condition is associated with BIRC6 p.Thr4064= (c.12192C>T)?

BIRC6 p.Thr4064= (c.12192C>T) is associated with BIRC6-related disorder (ClinVar).

How common is BIRC6 p.Thr4064= (c.12192C>T) in the general population?

BIRC6 p.Thr4064= (c.12192C>T) is low-frequency (popmax 1.49%, afr) (gnomAD).

BIRC6 p.Thr4064=

c.12192C>T · rs143909151 · VCV3038103

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 1.49%, afr)

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 -0.85	GERP -2.6, phastCons 0.003
Overall
CADD	6.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.49% African / African-American · 1,117/75,012 alleles

Filtering AF 1.42% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.39%

Overall 0.0806% 1,301/1,613,830 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.49%	67
Middle Eastern	0.231%	433
Admixed American	0.1%	1,000
Remaining individualsnot grpmax-eligible	0.0864%	1,157
European (non-Finnish)	0.00449%	22,261
East Asian	0.00223%	44,854
South Asian	0.0022%	45,532

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.Thr4064=
Coding: c.12192C>T
MANE Select: NM_016252
dbSNP: rs143909151
Type: single nucleotide variant
Location: chr2:32531452 (GRCh38)
Gene constraint: LOEUF 0.213 · pLI 1.00 (gnomAD)
Residue 4064: an α-helix; the ubiquitin-like domain

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-thr4064 (accessed [today's date]).

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