Is BIRC6 p.Ala2597Ser (c.7789G>T) pathogenic?

BIRC6 p.Ala2597Ser (c.7789G>T) is classified Uncertain significance in BIRC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-20). AlphaMissense: likely benign (0.2288); Absent from gnomAD v4.1.

How common is BIRC6 p.Ala2597Ser (c.7789G>T) in the general population?

BIRC6 p.Ala2597Ser (c.7789G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BIRC6 p.Ala2597Ser (c.7789G>T)?

AlphaMissense predicts likely benign (score 0.2288) — an in-silico prediction, not a clinical call.

BIRC6 p.Ala2597Ser

c.7789G>T · VCV4645971

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2288 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.2288	likely benign
REVEL	0.18	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 69 kb · p 0.5 · regional, not allelic
Overall
CADD	22.7	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 is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BIRC6
Protein: p.Ala2597Ser
Coding: c.7789G>T
MANE Select: NM_016252
Type: single nucleotide variant
Location: chr2:32485735 (GRCh38)
Gene constraint: LOEUF 0.213 · pLI 1.00 (gnomAD)
Residue 2597: an α-helix

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-ala2597ser (accessed [today's date]).

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