Is BIRC6 p.Ala3904Val (c.11711C>T) pathogenic?

BIRC6 p.Ala3904Val (c.11711C>T) is classified Uncertain significance in BIRC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-01). AlphaMissense: likely benign (0.1198); Ultra-rare (popmax 0.0151%, afr).

How common is BIRC6 p.Ala3904Val (c.11711C>T) in the general population?

BIRC6 p.Ala3904Val (c.11711C>T) is ultra-rare (popmax 0.0151%, afr) (gnomAD).

What do computational predictors say about BIRC6 p.Ala3904Val (c.11711C>T)?

AlphaMissense predicts likely benign (score 0.1198) — an in-silico prediction, not a clinical call.

BIRC6 p.Ala3904Val

c.11711C>T · VCV4209706

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1198 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0151%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.1198	likely benign
REVEL	0.176	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.9, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 34 kb · p 0.095 · regional, not allelic
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0151% African / African-American · 11/73,010 alleles

Filtering AF 0.00836% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00767%

Overall 0.00863% 135/1,564,822 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0151%	6,637
European (non-Finnish)	0.00968%	10,331
East Asian	0.00701%	14,256
Remaining individualsnot grpmax-eligible	0.00496%	20,153
Admixed American	0.0038%	26,349
Finnishnot grpmax-eligible	0.00323%	30,965
South Asian	0.00245%	40,804

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.Ala3904Val
Coding: c.11711C>T
MANE Select: NM_016252
Type: single nucleotide variant
Location: chr2:32524975 (GRCh38)
Gene constraint: LOEUF 0.213 · pLI 1.00 (gnomAD)
Residue 3904: the ubiquitin-like domain

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-ala3904val (accessed [today's date]).

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