Is BIRC7 p.Arg90Cys (c.268C>T) pathogenic?

BIRC7 p.Arg90Cys (c.268C>T) is classified Uncertain significance in BIRC7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-15). AlphaMissense: likely pathogenic (0.7281); Very rare (popmax 0.00268%, afr).

How common is BIRC7 p.Arg90Cys (c.268C>T) in the general population?

BIRC7 p.Arg90Cys (c.268C>T) is very rare (popmax 0.00268%, afr) (gnomAD).

What do computational predictors say about BIRC7 p.Arg90Cys (c.268C>T)?

AlphaMissense predicts likely pathogenic (score 0.7281) — an in-silico prediction, not a clinical call.

BIRC7 p.Arg90Cys

c.268C>T · VCV3824414

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7281 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00268%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7281	likely pathogenic
REVEL	0.797	moderately pathogenic-leaning
SaProt	LLR -7.69	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.88	GERP 0.55, phastCons 0.99
Regional constraint	o/e 1.02	unconstrained · MANE · 3,505 bp · p 0.7 · regional, not allelic
Overall
CADD	23.2	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 0.00268% African / African-American · 2/74,560 alleles

Filtering AF 0.000964% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000796%

Overall 0.00233% 37/1,591,286 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0457%	2,190
Remaining individualsnot grpmax-eligible	0.00326%	30,674
African / African-Americangrpmax	0.00268%	37,280
Admixed American	0.0017%	58,828
European (non-Finnish)	0.00154%	64,805
South Asian	0.00112%	89,124

Ashkenazi Jewish 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: BIRC7
Protein: p.Arg90Cys
Coding: c.268C>T
MANE Select: NM_139317
Type: single nucleotide variant
Location: chr20:63236364 (GRCh38)
Gene constraint: LOEUF 1.18 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.40 · 13 PDB
Residue 90: 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-arg90cys (accessed [today's date]).

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