Is BCL2L15 p.Ser4Pro (c.10T>C) pathogenic?

BCL2L15 p.Ser4Pro (c.10T>C) is classified Likely benign in BCL2L15 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-14). AlphaMissense: likely benign (0.0409); Ultra-rare (popmax 0.0233%, amr).

How common is BCL2L15 p.Ser4Pro (c.10T>C) in the general population?

BCL2L15 p.Ser4Pro (c.10T>C) is ultra-rare (popmax 0.0233%, amr) (gnomAD).

What do computational predictors say about BCL2L15 p.Ser4Pro (c.10T>C)?

AlphaMissense predicts likely benign (score 0.0409) — an in-silico prediction, not a clinical call.

BCL2L15 p.Ser4Pro

c.10T>C · VCV4201852

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0409 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0233%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0409	likely benign
REVEL	0.046	moderately benign-leaning
SaProt	LLR -5.57	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.3	GERP 0.32, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 6,249 bp · p 0.13 · regional, not allelic
Overall
CADD	9.528	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 0.0233% Admixed American · 14/60,016 alleles

Filtering AF 0.0141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0112%

Overall 0.000958% 14/1,461,792 alleles · ultra-rare

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: BCL2L15
Protein: p.Ser4Pro
Coding: c.10T>C
Type: single nucleotide variant
Location: chr1:113887366 (GRCh38)

Full BCL2L15 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/bcl2l15-p-ser4pro (accessed [today's date]).

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