Is BIRC7 p.Pro266Ser (c.796C>T) pathogenic?

BIRC7 p.Pro266Ser (c.796C>T) is classified Uncertain significance in BIRC7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-04). AlphaMissense: likely pathogenic (0.8838); Ultra-rare (popmax 0.0533%, amr).

How common is BIRC7 p.Pro266Ser (c.796C>T) in the general population?

BIRC7 p.Pro266Ser (c.796C>T) is ultra-rare (popmax 0.0533%, amr) (gnomAD).

What do computational predictors say about BIRC7 p.Pro266Ser (c.796C>T)?

AlphaMissense predicts likely pathogenic (score 0.8838) — an in-silico prediction, not a clinical call.

BIRC7 p.Pro266Ser

c.796C>T · rs755790359 · VCV3134111

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8838 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0533%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8838	likely pathogenic · top 9% in BIRC7
REVEL	0.829	moderately pathogenic-leaning
SaProt	LLR -13.13	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7	GERP 2.1, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 3,505 bp · p 0.7 · regional, not allelic
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0533% Admixed American · 32/60,008 alleles

Filtering AF 0.0387% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0339%

Overall 0.00227% 33/1,454,048 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0533%	1,875
South Asian	0.0011%	91,070

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: BIRC7
Protein: p.Pro266Ser
Coding: c.796C>T
MANE Select: NM_139317
dbSNP: rs755790359
Type: single nucleotide variant
Location: chr20:63239504 (GRCh38)
Gene constraint: LOEUF 1.18 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.40 · 13 PDB

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-pro266ser (accessed [today's date]).

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