Is BCL2L2 p.Arg161Pro (c.482G>C) pathogenic?

BCL2L2 p.Arg161Pro (c.482G>C) is classified Uncertain significance in BCL2L2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-05). AlphaMissense: likely pathogenic (0.5655); Absent from gnomAD v4.1.

How common is BCL2L2 p.Arg161Pro (c.482G>C) in the general population?

BCL2L2 p.Arg161Pro (c.482G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BCL2L2 p.Arg161Pro (c.482G>C)?

AlphaMissense predicts likely pathogenic (score 0.5655) — an in-silico prediction, not a clinical call.

BCL2L2 p.Arg161Pro

c.482G>C · rs200041771 · VCV3133423

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5655 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.5655	likely pathogenic
REVEL	0.293	indeterminate
SaProt	LLR -11.29	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 0.52, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 1,194 bp · p 1.7e-05 · regional, not allelic
Overall
CADD	24.9	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

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: BCL2L2
Protein: p.Arg161Pro
Coding: c.482G>C
MANE Select: NM_004050
dbSNP: rs200041771
Type: single nucleotide variant
Location: chr14:23308865 (GRCh38)
Gene constraint: LOEUF 0.883 · pLI 0.20 (gnomAD)
Structure: AlphaFold pLDDT 82.27 · 5 PDB
Residue 161: an α-helix

Full BCL2L2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BCL2L2 p.Arg161His Uncertain significance ★ ⚠ same residue
BCL2L2 p.Ala149Val Uncertain significance ★ ⚠ same type
BCL2L2 p.Ala159Ser Uncertain significance ★ ⚠ same type
BCL2L2 p.Ala159Val Uncertain significance ★ ⚠ same type
BCL2L2 p.Ala191Gly Uncertain significance ★ ⚠ same type
BCL2L2 p.Arg160Gln Uncertain significance ★ ⚠ same type
BCL2L2 p.Thr175Ala Uncertain significance ★ ⚠ same type
BCL2L2 p.Val186Ile 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/bcl2l2-p-arg161pro (accessed [today's date]).

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