Is BCL2 p.Thr7= (c.21A>G) pathogenic?

BCL2 p.Thr7= (c.21A>G) is classified Benign in BCL2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-16). Common (popmax 43.1%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with BCL2-related disorder.

What condition is associated with BCL2 p.Thr7= (c.21A>G)?

BCL2 p.Thr7= (c.21A>G) is associated with BCL2-related disorder (ClinVar).

BCL2 p.Thr7=

Q: How common is BCL2 p.Thr7= (c.21A>G) in the general population?

BCL2 p.Thr7= (c.21A>G) is common (popmax 43.1%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.21A>G · rs1801018 · VCV3060318

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 43.1%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

BCL2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.037	GERP -2.5, phastCons 0.97
Overall
CADD	8.231	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 43.1% European (non-Finnish) · 508,232/1,178,952 alleles

Filtering AF 43% ClinGen BA1/BS1 input FAF95, joint · FAF99 43%

Overall 39.8% 641,749/1,612,024 alleles · common exomes 593,323/1,459,826 · genomes 48,426/152,198 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	52.3%	2
Finnishnot grpmax-eligible	45.8%	2
European (non-Finnish)grpmax	43.1%	2
Admixed American	40.8%	2
Middle Eastern	39%	3
Remaining individualsnot grpmax-eligible	37.1%	3
South Asian	36.7%	3
Ashkenazi Jewishnot grpmax-eligible	34.7%	3
East Asian	10.5%	10
African / African-American	7.49%	13

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: BCL2
Protein: p.Thr7=
Coding: c.21A>G
MANE Select: NM_000633
dbSNP: rs1801018
Type: single nucleotide variant
Location: chr18:63318646 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 74.21 · 63 PDB
Residue 7: a UniProt-annotated variant site (sequence variant)

Full BCL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

BCL2-related disorder

Similar variants

BCL2 p.Ala100= Benign same condition
BCL2 p.Ala113Asp Uncertain significance ★ ⚠ same type
BCL2 p.Gly79Asp Uncertain significance ★ ⚠ same type
BCL2 p.Met166Leu Uncertain significance ★ ⚠ same type
BCL2 p.Phe150Leu Uncertain significance ★ ⚠ same type
BCL2 p.Phe153Tyr Uncertain significance ★ ⚠ same type
BCL2 p.Ser24Leu Uncertain significance ★ ⚠ same type
BCL2 p.Phe153= Likely benign ★ 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/bcl2-p-thr7 (accessed [today's date]).

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