Is BCL7C p.Pro141Arg (c.422C>G) pathogenic?

BCL7C p.Pro141Arg (c.422C>G) is classified Uncertain significance in BCL7C (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-28). AlphaMissense: likely benign (0.2657); Very rare (popmax 0.00462%, nfe).

How common is BCL7C p.Pro141Arg (c.422C>G) in the general population?

BCL7C p.Pro141Arg (c.422C>G) is very rare (popmax 0.00462%, nfe) (gnomAD).

What do computational predictors say about BCL7C p.Pro141Arg (c.422C>G)?

AlphaMissense predicts likely benign (score 0.2657) — an in-silico prediction, not a clinical call.

BCL7C p.Pro141Arg

c.422C>G · VCV3480179

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2657 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00462%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2657	likely benign
REVEL	0.437	indeterminate
SaProt	LLR -7.79	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 6,076 bp · p 0.035 · regional, not allelic
Overall
CADD	25.0	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 0.00462% European (non-Finnish) · 54/1,168,330 alleles

Filtering AF 0.00362% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00324%

Overall 0.00354% 56/1,582,204 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00462%	21,636
Admixed American	0.0019%	52,692
Remaining individualsnot grpmax-eligible	0.00164%	60,934

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.Pro141Arg
Coding: c.422C>G
MANE Select: NM_004765
Type: single nucleotide variant
Location: chr16:30892606 (GRCh38)
Gene constraint: LOEUF 0.546 · pLI 0.94 (gnomAD)
Structure: AlphaFold pLDDT 63.71
Residue 141: the 'disordered' region

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

Similar variants

BCL7C p.Pro141Gln Uncertain significance ★ ⚠ same residue
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

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-pro141arg (accessed [today's date]).

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