Is BIRC6 p.Pro628= (c.1884G>A) pathogenic?

BIRC6 p.Pro628= (c.1884G>A) is classified Likely benign in BIRC6 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-12-18). Ultra-rare (popmax 0.02%, afr); Associated with BIRC6-related disorder.

What condition is associated with BIRC6 p.Pro628= (c.1884G>A)?

BIRC6 p.Pro628= (c.1884G>A) is associated with BIRC6-related disorder (ClinVar).

How common is BIRC6 p.Pro628= (c.1884G>A) in the general population?

BIRC6 p.Pro628= (c.1884G>A) is ultra-rare (popmax 0.02%, afr) (gnomAD).

BIRC6 p.Pro628=

c.1884G>A · rs148244969 · VCV3048271

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, 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 -3.1	GERP -5.4
Overall
CADD	7.485	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.02% African / African-American · 15/75,034 alleles

Filtering AF 0.0123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00988%

Overall 0.00539% 87/1,613,928 alleles · ultra-rare exomes 67/1,461,660 · genomes 20/152,268 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.02%	5,002
Middle Eastern	0.0165%	6,062
Admixed American	0.0133%	7,502
European (non-Finnish)	0.00492%	20,343
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602
East Asian	0.00223%	44,884
Remaining individualsnot grpmax-eligible	0.0016%	62,486
Finnishnot grpmax-eligible	0.00156%	63,996
South Asian	0.0011%	91,058

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.Pro628=
Coding: c.1884G>A
MANE Select: NM_016252
dbSNP: rs148244969
Type: single nucleotide variant
Location: chr2:32415175 (GRCh38)
Gene constraint: LOEUF 0.213 · pLI 1.00 (gnomAD)
Residue 628: a β-strand

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-pro628 (accessed [today's date]).

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