Is BIRC6 p.Pro2783= (c.8349T>C) pathogenic?

BIRC6 p.Pro2783= (c.8349T>C) is classified Benign in BIRC6 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-02-19). Common (popmax 7.69%, afr) — too common for a highly-penetrant pathogenic allele; Associated with BIRC6-related disorder.

What condition is associated with BIRC6 p.Pro2783= (c.8349T>C)?

BIRC6 p.Pro2783= (c.8349T>C) is associated with BIRC6-related disorder (ClinVar).

BIRC6 p.Pro2783=

Q: How common is BIRC6 p.Pro2783= (c.8349T>C) in the general population?

BIRC6 p.Pro2783= (c.8349T>C) is common (popmax 7.69%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.8349T>C · rs61754197 · VCV3038366

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 7.69%, 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 0.74	GERP -3.5, phastCons 0.95
Overall
CADD	5.764	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.69% African / African-American · 5,764/74,956 alleles

Filtering AF 7.52% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.46%

Overall 2.37% 38,152/1,608,706 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.69%	13
Middle Eastern	4.69%	21
Ashkenazi Jewishnot grpmax-eligible	3.37%	30
Remaining individualsnot grpmax-eligible	2.63%	38
Amishnot grpmax-eligible	2.52%	40
European (non-Finnish)	2.25%	44
Admixed American	2.11%	47
South Asian	1.63%	61
Finnishnot grpmax-eligible	0.392%	255
East Asian	0.0179%	5,590

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.Pro2783=
Coding: c.8349T>C
MANE Select: NM_016252
dbSNP: rs61754197
Type: single nucleotide variant
Location: chr2:32493548 (GRCh38)
Gene constraint: LOEUF 0.213 · pLI 1.00 (gnomAD)
Residue 2783: 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-pro2783 (accessed [today's date]).

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