Is BCL2L14 p.Lys89Ile (c.266A>T) pathogenic?

BCL2L14 p.Lys89Ile (c.266A>T) is classified Uncertain significance in BCL2L14 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-14). AlphaMissense: likely pathogenic (0.7029); Very rare (popmax 0.000424%, nfe).

How common is BCL2L14 p.Lys89Ile (c.266A>T) in the general population?

BCL2L14 p.Lys89Ile (c.266A>T) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about BCL2L14 p.Lys89Ile (c.266A>T)?

AlphaMissense predicts likely pathogenic (score 0.7029) — an in-silico prediction, not a clinical call.

BCL2L14 p.Lys89Ile

c.266A>T · VCV3823938

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7029 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7029	likely pathogenic
REVEL	0.224	benign-leaning
SaProt	LLR -9.47	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.2	GERP 0.098, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 20 kb · p 0.78 · regional, not allelic
Overall
CADD	23.8	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 0.000424% European (non-Finnish) · 5/1,180,044 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,614,224 alleles · very rare exomes 5/1,461,888 · genomes 0/152,336 · 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: BCL2L14
Protein: p.Lys89Ile
Coding: c.266A>T
MANE Select: NM_138723
Type: single nucleotide variant
Location: chr12:12079571 (GRCh38)
Gene constraint: LOEUF 0.96 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.91

Full BCL2L14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BCL2L14 p.Glu69= Benign ★★ same type
BCL2L14 p.Ala280Thr Uncertain significance ★ ⚠ same type
BCL2L14 p.Ala284Ser Uncertain significance ★ ⚠ same type
BCL2L14 p.Ala28Thr Uncertain significance ★ ⚠ same type
BCL2L14 p.Arg132Gly Uncertain significance ★ ⚠ same type
BCL2L14 p.Arg132Ser Uncertain significance ★ ⚠ same type
BCL2L14 p.Arg156Gly Uncertain significance ★ ⚠ same type
BCL2L14 p.Arg292Ser 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/bcl2l14-p-lys89ile (accessed [today's date]).

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