Is BIRC2 p.Val590Ile (c.1768G>A) pathogenic?

BIRC2 p.Val590Ile (c.1768G>A) is classified Uncertain significance in BIRC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-20). AlphaMissense: ambiguous (0.38); Ultra-rare (popmax 0.0394%, nfe).

How common is BIRC2 p.Val590Ile (c.1768G>A) in the general population?

BIRC2 p.Val590Ile (c.1768G>A) is ultra-rare (popmax 0.0394%, nfe) (gnomAD).

What do computational predictors say about BIRC2 p.Val590Ile (c.1768G>A)?

AlphaMissense predicts ambiguous (score 0.38) — an in-silico prediction, not a clinical call.

BIRC2 p.Val590Ile

c.1768G>A · rs201982932 · VCV2365875

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.38 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0394%, nfe)

Computational evidence

Protein change
AlphaMissense	0.38	ambiguous
REVEL	0.469	indeterminate
SaProt	LLR -8.83	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 302 bp · p 0.00049 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0394% European (non-Finnish) · 465/1,179,822 alleles

Filtering AF 0.0365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0352%

Overall 0.0294% 475/1,613,688 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0394%	2,537
Remaining individualsnot grpmax-eligible	0.0112%	8,922
African / African-American	0.00401%	24,966

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: BIRC2
Protein: p.Val590Ile
Coding: c.1768G>A
MANE Select: NM_001166
dbSNP: rs201982932
Type: single nucleotide variant
Location: chr11:102378094 (GRCh38)
Gene constraint: LOEUF 0.381 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.08 · 29 PDB
Residue 590: a β-strand

Full BIRC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BIRC2 p.Ala506Val Benign ★★ same type
BIRC2 p.Ala186Thr Uncertain significance ★ ⚠ same type
BIRC2 p.Ala388Thr Uncertain significance ★ ⚠ same type
BIRC2 p.Ala58Ser Uncertain significance ★ ⚠ same type
BIRC2 p.Arg164Lys Uncertain significance ★ ⚠ same type
BIRC2 p.Arg241Gln Uncertain significance ★ ⚠ same type
BIRC2 p.Arg300Cys Uncertain significance ★ ⚠ same type
BIRC2 p.Arg338Gln Uncertain significance ★ ⚠ 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/birc2-p-val590ile (accessed [today's date]).

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