Is BIRC7 p.Arg290Cys (c.868C>T) pathogenic?

BIRC7 p.Arg290Cys (c.868C>T) is classified Uncertain significance in BIRC7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-27). AlphaMissense: likely benign (0.1187); Very rare (popmax 0.0088%, sas).

How common is BIRC7 p.Arg290Cys (c.868C>T) in the general population?

BIRC7 p.Arg290Cys (c.868C>T) is very rare (popmax 0.0088%, sas) (gnomAD).

What do computational predictors say about BIRC7 p.Arg290Cys (c.868C>T)?

AlphaMissense predicts likely benign (score 0.1187) — an in-silico prediction, not a clinical call.

BIRC7 p.Arg290Cys

c.868C>T · rs148392338 · VCV3134113

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1187 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0088%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1187	likely benign
REVEL	0.24	benign-leaning
SaProt	LLR -10.00	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.45	GERP -3.9
Regional constraint	o/e 1.02	unconstrained · MANE · 3,505 bp · p 0.7 · regional, not allelic
Overall
CADD	12.53	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

Grpmax group 0.0088% South Asian · 8/90,876 alleles

Filtering AF 0.00438% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00313%

Overall 0.002% 32/1,599,922 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0088%	11,360
African / African-American	0.00802%	12,475
Remaining individualsnot grpmax-eligible	0.00321%	31,109
East Asian	0.00223%	44,834
European (non-Finnish)	0.00127%	78,612

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.Arg290Cys
Coding: c.868C>T
MANE Select: NM_139317
dbSNP: rs148392338
Type: single nucleotide variant
Location: chr20:63239576 (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-arg290cys (accessed [today's date]).

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