Is BIRC7 p.Leu89Ser (c.266T>C) pathogenic?

BIRC7 p.Leu89Ser (c.266T>C) is classified Uncertain significance in BIRC7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-15). AlphaMissense: ambiguous (0.4073); Absent from gnomAD v4.1.

How common is BIRC7 p.Leu89Ser (c.266T>C) in the general population?

BIRC7 p.Leu89Ser (c.266T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BIRC7 p.Leu89Ser (c.266T>C)?

AlphaMissense predicts ambiguous (score 0.4073) — an in-silico prediction, not a clinical call.

BIRC7 p.Leu89Ser

c.266T>C · VCV3824415

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4073 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4073	ambiguous
REVEL	0.112	moderately benign-leaning
SaProt	LLR -5.00	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 1.7, phastCons 0.98
Regional constraint	o/e 1.02	unconstrained · MANE · 3,505 bp · p 0.7 · regional, not allelic
Overall
CADD	19.05	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

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: BIRC7
Protein: p.Leu89Ser
Coding: c.266T>C
MANE Select: NM_139317
Type: single nucleotide variant
Location: chr20:63236362 (GRCh38)
Gene constraint: LOEUF 1.18 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.40 · 13 PDB
Residue 89: an α-helix

Full BIRC7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BIRC7 p.Ala187Gly Benign ★★ same type
BIRC7 p.Pro204Ser Benign ★★ same type
BIRC7 p.Ala273Val Uncertain significance ★ ⚠ same type
BIRC7 p.Arg156Trp Uncertain significance ★ ⚠ same type
BIRC7 p.Arg160Lys Uncertain significance ★ ⚠ same type
BIRC7 p.Arg244Trp Uncertain significance ★ ⚠ same type
BIRC7 p.Arg245Gln Uncertain significance ★ ⚠ same type
BIRC7 p.Arg245Trp 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/birc7-p-leu89ser (accessed [today's date]).

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