Is BIRC6 p.Ala4566Val (c.13697C>T) pathogenic?

BIRC6 p.Ala4566Val (c.13697C>T) is classified Uncertain significance in BIRC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-27). AlphaMissense: likely benign (0.2048); Ultra-rare (popmax 0.0164%, mid).

How common is BIRC6 p.Ala4566Val (c.13697C>T) in the general population?

BIRC6 p.Ala4566Val (c.13697C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about BIRC6 p.Ala4566Val (c.13697C>T)?

AlphaMissense predicts likely benign (score 0.2048) — an in-silico prediction, not a clinical call.

BIRC6 p.Ala4566Val

c.13697C>T · VCV3480708

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2048 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Computational evidence

Protein change
AlphaMissense	0.2048	likely benign
REVEL	0.313	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 55 kb · p 4.9e-05 · regional, not allelic
Overall
CADD	22.9	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00312%

Overall 0.00112% 18/1,613,592 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
South Asian	0.00878%	11,384
East Asian	0.00223%	44,884
European (non-Finnish)	0.000678%	147,462

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.Ala4566Val
Coding: c.13697C>T
MANE Select: NM_016252
Type: single nucleotide variant
Location: chr2:32597835 (GRCh38)
Gene constraint: LOEUF 0.213 · pLI 1.00 (gnomAD)

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

Similar variants

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
BIRC6 p.Asp4607= 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-ala4566val (accessed [today's date]).

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