Is BIRC7 p.Arg156Trp (c.466C>T) pathogenic?

BIRC7 p.Arg156Trp (c.466C>T) is classified Uncertain significance in BIRC7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-18). AlphaMissense: likely benign (0.0962); Rare (popmax 0.128%, sas).

How common is BIRC7 p.Arg156Trp (c.466C>T) in the general population?

BIRC7 p.Arg156Trp (c.466C>T) is rare (popmax 0.128%, sas) (gnomAD).

What do computational predictors say about BIRC7 p.Arg156Trp (c.466C>T)?

AlphaMissense predicts likely benign (score 0.0962) — an in-silico prediction, not a clinical call.

BIRC7 p.Arg156Trp

c.466C>T · VCV3991589

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0962 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.128%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0962	likely benign
REVEL	0.084	moderately benign-leaning
SaProt	LLR -7.93	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.28 · evaluated, not missing
Pangolin	Δ0.21	loss · gain 0.00 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 0.64	GERP -0.73
Regional constraint	o/e 1.02	unconstrained · MANE · 3,505 bp · p 0.7 · regional, not allelic
Overall
CADD	23.3	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 and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.128% South Asian · 117/91,086 alleles

Filtering AF 0.11% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.102%

Overall 0.00931% 150/1,611,930 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.128%	779
Remaining individualsnot grpmax-eligible	0.008%	12,497
Admixed American	0.005%	20,001
Finnishnot grpmax-eligible	0.00485%	20,627
East Asian	0.00446%	22,441
European (non-Finnish)	0.00169%	58,998

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.Arg156Trp
Coding: c.466C>T
MANE Select: NM_139317
Type: single nucleotide variant
Location: chr20:63238412 (GRCh38)
Gene constraint: LOEUF 1.18 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.40 · 13 PDB
Residue 156: 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.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
BIRC7 p.Arg290Cys 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-arg156trp (accessed [today's date]).

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