Is BIRC6 p.Asp2480Tyr (c.7438G>T) pathogenic?

BIRC6 p.Asp2480Tyr (c.7438G>T) is classified Uncertain significance in BIRC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-13). AlphaMissense: ambiguous (0.4743); Very rare (popmax 0.00168%, amr).

How common is BIRC6 p.Asp2480Tyr (c.7438G>T) in the general population?

BIRC6 p.Asp2480Tyr (c.7438G>T) is very rare (popmax 0.00168%, amr) (gnomAD).

What do computational predictors say about BIRC6 p.Asp2480Tyr (c.7438G>T)?

AlphaMissense predicts ambiguous (score 0.4743) — an in-silico prediction, not a clinical call.

BIRC6 p.Asp2480Tyr

c.7438G>T · VCV3824383

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4743 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00168%, amr)

Computational evidence

Protein change
AlphaMissense	0.4743	ambiguous
REVEL	0.404	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 69 kb · p 0.5 · regional, not allelic
Overall
CADD	25.4	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 0.00168% Admixed American · 1/59,476 alleles

Filtering AF 0.00088% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000719%

Overall 0.00149% 24/1,609,068 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00964%	10,374
Admixed Americangrpmax	0.00168%	59,476
European (non-Finnish)	0.00144%	69,254

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp2480Tyr
Coding: c.7438G>T
MANE Select: NM_016252
Type: single nucleotide variant
Location: chr2:32481349 (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-asp2480tyr (accessed [today's date]).

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