Is BIRC6 p.Asp481Glu (c.1443C>A) pathogenic?

BIRC6 p.Asp481Glu (c.1443C>A) is classified Uncertain significance in BIRC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-14). AlphaMissense: likely pathogenic (0.5685); Very rare (popmax 0.00134%, afr).

How common is BIRC6 p.Asp481Glu (c.1443C>A) in the general population?

BIRC6 p.Asp481Glu (c.1443C>A) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about BIRC6 p.Asp481Glu (c.1443C>A)?

AlphaMissense predicts likely pathogenic (score 0.5685) — an in-silico prediction, not a clinical call.

BIRC6 p.Asp481Glu

c.1443C>A · VCV3991542

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5685 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Computational evidence

Protein change
AlphaMissense	0.5685	likely pathogenic
REVEL	0.378	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 0.43, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 30 kb · p 0.15 · regional, not allelic
Overall
CADD	21.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,758 alleles

Overall 0.000124% 2/1,609,764 alleles · very rare exomes 1/1,457,602 · genomes 1/152,162 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,758
European (non-Finnish)	8.49e-05%	1,177,414

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.Asp481Glu
Coding: c.1443C>A
MANE Select: NM_016252
Type: single nucleotide variant
Location: chr2:32406523 (GRCh38)
Gene constraint: LOEUF 0.213 · pLI 1.00 (gnomAD)
Residue 481: the 'disordered' region

Full BIRC6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BIRC6 p.Asp481His Uncertain significance ★ same residue
BIRC6 p.Gln853Arg Uncertain significance ★★ ⚠ same type
BIRC6 p.Glu4506Asp Uncertain significance ★★ ⚠ same type
BIRC6 c.7409-6T>C Likely benign ★★ same type
BIRC6 p.Ala1549= Benign ★★ same type
BIRC6 p.Ala3622Val Likely benign ★★ same type
BIRC6 p.Ala4466= Benign/Likely benign ★★ same type
BIRC6 p.Arg4605= Benign ★★ same type

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-asp481glu (accessed [today's date]).

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