Is BCL7B p.Ala199= (c.597G>C) pathogenic?

BCL7B p.Ala199= (c.597G>C) is classified Likely benign in BCL7B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-01). Rare (popmax 0.825%, mid).

How common is BCL7B p.Ala199= (c.597G>C) in the general population?

BCL7B p.Ala199= (c.597G>C) is rare (popmax 0.825%, mid) (gnomAD).

BCL7B p.Ala199=

c.597G>C · rs142166738 · VCV2657554

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.825%, mid)

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 -15	GERP -3.1
Overall
CADD	0.018	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.825% Middle Eastern · 50/6,058 alleles

Filtering AF 0.643% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.578%

Overall 0.36% 5,809/1,614,024 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.49%	67
Middle Easterngrpmax	0.825%	121
Remaining individualsnot grpmax-eligible	0.398%	251
European (non-Finnish)	0.394%	254
Finnishnot grpmax-eligible	0.27%	370
South Asian	0.141%	712
Admixed American	0.127%	790
African / African-American	0.0586%	1,706

Ashkenazi Jewish 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: BCL7B
Protein: p.Ala199=
Coding: c.597G>C
MANE Select: NM_001707
dbSNP: rs142166738
Type: single nucleotide variant
Location: chr7:73537310 (GRCh38)
Gene constraint: LOEUF 0.867 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 63.91 · 3 PDB
Residue 199: the 'disordered' region

Full BCL7B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BCL7B p.Ala155Gly Uncertain significance ★ ⚠ same type
BCL7B p.Arg130Cys Uncertain significance ★ ⚠ same type
BCL7B p.Arg187Pro Uncertain significance ★ ⚠ same type
BCL7B p.His125Leu Uncertain significance ★ ⚠ same type
BCL7B p.His125Pro Uncertain significance ★ ⚠ same type
BCL7B p.Leu83Pro Uncertain significance ★ ⚠ same type
BCL7B p.Phe73Leu Uncertain significance ★ ⚠ same type
BCL7B p.Pro115Leu 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/bcl7b-p-ala199 (accessed [today's date]).

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