Is BNC1 p.Arg792Cys (c.2374C>T) pathogenic?

BNC1 p.Arg792Cys (c.2374C>T) is classified Uncertain significance in BNC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-05). AlphaMissense: likely benign (0.0766); Ultra-rare (popmax 0.035%, amr).

How common is BNC1 p.Arg792Cys (c.2374C>T) in the general population?

BNC1 p.Arg792Cys (c.2374C>T) is ultra-rare (popmax 0.035%, amr) (gnomAD).

What do computational predictors say about BNC1 p.Arg792Cys (c.2374C>T)?

AlphaMissense predicts likely benign (score 0.0766) — an in-silico prediction, not a clinical call.

BNC1 p.Arg792Cys

c.2374C>T · rs201142132 · VCV3134644

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0766 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.035%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0766	likely benign
REVEL	0.072	moderately benign-leaning
SaProt	LLR -8.01	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 5.5	GERP 2.4, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 6,564 bp · p 0.028 · regional, not allelic
Overall
CADD	20.7	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 0.035% Admixed American · 21/59,998 alleles

Filtering AF 0.0234% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0197%

Overall 0.00744% 120/1,613,558 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.035%	2,857
Middle Eastern	0.0329%	3,040
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,401
East Asian	0.0134%	7,477
Remaining individualsnot grpmax-eligible	0.0112%	8,924
European (non-Finnish)	0.00644%	15,521
African / African-American	0.00267%	37,465
South Asian	0.0022%	45,539

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: BNC1
Protein: p.Arg792Cys
Coding: c.2374C>T
MANE Select: NM_001717
dbSNP: rs201142132
Type: single nucleotide variant
Location: chr15:83258053 (GRCh38)
Gene constraint: LOEUF 0.212 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.85

Full BNC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BNC1 p.Ser192= Benign ★★ same type
BNC1 p.Ser787Gly Benign ★★ same type
BNC1 p.Thr758Ile Likely pathogenic ★ ⚠ same type
BNC1 p.Ala13Val Uncertain significance ★ ⚠ same type
BNC1 p.Ala147Thr Uncertain significance ★ ⚠ same type
BNC1 p.Ala16Val Uncertain significance ★ ⚠ same type
BNC1 p.Ala693Val Uncertain significance ★ ⚠ same type
BNC1 p.Ala804Ser 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/bnc1-p-arg792cys (accessed [today's date]).

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