Is BCL2L13 p.Ala135Pro (c.403G>C) pathogenic?

BCL2L13 p.Ala135Pro (c.403G>C) is classified Uncertain significance in BCL2L13 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-24). AlphaMissense: ambiguous (0.4875); Very rare (popmax 0.0022%, nfe).

How common is BCL2L13 p.Ala135Pro (c.403G>C) in the general population?

BCL2L13 p.Ala135Pro (c.403G>C) is very rare (popmax 0.0022%, nfe) (gnomAD).

What do computational predictors say about BCL2L13 p.Ala135Pro (c.403G>C)?

AlphaMissense predicts ambiguous (score 0.4875) — an in-silico prediction, not a clinical call.

BCL2L13 p.Ala135Pro

c.403G>C · rs773293223 · VCV2512106

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4875 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4875	ambiguous
REVEL	0.257	benign-leaning
SaProt	LLR -11.09	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.87	GERP -3.5, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 72 kb · p 0.0031 · regional, not allelic
Overall
CADD	16.58	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 0.0022% European (non-Finnish) · 26/1,179,738 alleles

Filtering AF 0.00153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0013%

Overall 0.00161% 26/1,613,586 alleles · very rare exomes 25/1,461,448 · genomes 1/152,138 · joint denominator

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: BCL2L13
Protein: p.Ala135Pro
Coding: c.403G>C
MANE Select: NM_015367
dbSNP: rs773293223
Type: single nucleotide variant
Location: chr22:17696157 (GRCh38)
Gene constraint: LOEUF 0.738 · pLI 0.25 (gnomAD)
Structure: AlphaFold pLDDT 65.27

Full BCL2L13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BCL2L13 p.Ile46Thr Benign ★★ same type
BCL2L13 p.Ala325Pro Uncertain significance ★ ⚠ same type
BCL2L13 p.Ala341Asp Uncertain significance ★ ⚠ same type
BCL2L13 p.Ala416Pro Uncertain significance ★ ⚠ same type
BCL2L13 p.Ala467Thr Uncertain significance ★ ⚠ same type
BCL2L13 p.Arg137Gln Uncertain significance ★ ⚠ same type
BCL2L13 p.Arg137Gly Uncertain significance ★ ⚠ same type
BCL2L13 p.Arg169Thr 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/bcl2l13-p-ala135pro (accessed [today's date]).

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