Is BIRC6 p.Leu679= (c.2037A>G) pathogenic?

BIRC6 p.Leu679= (c.2037A>G) is classified Benign in BIRC6 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-02-19). Common (popmax 11.9%, afr) — too common for a highly-penetrant pathogenic allele; Associated with BIRC6-related disorder.

What condition is associated with BIRC6 p.Leu679= (c.2037A>G)?

BIRC6 p.Leu679= (c.2037A>G) is associated with BIRC6-related disorder (ClinVar).

BIRC6 p.Leu679=

Q: How common is BIRC6 p.Leu679= (c.2037A>G) in the general population?

BIRC6 p.Leu679= (c.2037A>G) is common (popmax 11.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2037A>G · rs34417238 · VCV3057184

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 11.9%, afr) — too common for a highly-penetrant pathogenic allele

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 5.7	GERP 1.2, phastCons 1
Overall
CADD	8.973	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 11.9% African / African-American · 8,903/75,022 alleles

Filtering AF 11.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 11.6%

Overall 1.75% 28,220/1,613,978 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	11.9%	8
Amishnot grpmax-eligible	2.85%	35
Remaining individualsnot grpmax-eligible	1.95%	51
Middle Eastern	1.65%	61
Admixed American	1.59%	63
European (non-Finnish)	1.3%	77
South Asian	1.22%	82
Ashkenazi Jewishnot grpmax-eligible	1.14%	88
Finnishnot grpmax-eligible	0.342%	292
East Asian	0.0356%	2,805

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.Leu679=
Coding: c.2037A>G
MANE Select: NM_016252
dbSNP: rs34417238
Type: single nucleotide variant
Location: chr2:32415328 (GRCh38)
Gene constraint: LOEUF 0.213 · pLI 1.00 (gnomAD)

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-leu679 (accessed [today's date]).

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