Is BCL7C p.Ser69Cys (c.206C>G) pathogenic?

BCL7C p.Ser69Cys (c.206C>G) is classified Uncertain significance in BCL7C (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-15). AlphaMissense: likely benign (0.123); Ultra-rare (popmax 0.0657%, mid).

How common is BCL7C p.Ser69Cys (c.206C>G) in the general population?

BCL7C p.Ser69Cys (c.206C>G) is ultra-rare (popmax 0.0657%, mid) (gnomAD).

What do computational predictors say about BCL7C p.Ser69Cys (c.206C>G)?

AlphaMissense predicts likely benign (score 0.123) — an in-silico prediction, not a clinical call.

BCL7C p.Ser69Cys

c.206C>G · VCV3991034

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.123 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0657%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.123	likely benign
REVEL	0.061	moderately benign-leaning
SaProt	LLR -8.59	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 6,076 bp · p 0.035 · regional, not allelic
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0657% Middle Eastern · 4/6,084 alleles

Filtering AF 0.0224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.00192% 31/1,612,982 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0657%	1,521
Admixed American	0.0117%	8,568
Remaining individualsnot grpmax-eligible	0.0112%	8,924
European (non-Finnish)	0.0011%	90,767

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: BCL7C
Protein: p.Ser69Cys
Coding: c.206C>G
MANE Select: NM_004765
Type: single nucleotide variant
Location: chr16:30892914 (GRCh38)
Gene constraint: LOEUF 0.546 · pLI 0.94 (gnomAD)
Structure: AlphaFold pLDDT 63.71
Residue 69: the 'disordered' region

Full BCL7C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BCL7C p.Arg209His Uncertain significance ★ ⚠ same type
BCL7C p.Arg70His Uncertain significance ★ ⚠ same type
BCL7C p.Arg74Cys Uncertain significance ★ ⚠ same type
BCL7C p.Arg75Gln Uncertain significance ★ ⚠ same type
BCL7C p.Arg82Gln Uncertain significance ★ ⚠ same type
BCL7C p.Asp94Gly Uncertain significance ★ ⚠ same type
BCL7C p.Glu146Gln Uncertain significance ★ ⚠ same type
BCL7C p.Glu179Lys 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/bcl7c-p-ser69cys (accessed [today's date]).

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