Is BNC1 p.Arg24Trp (c.70C>T) pathogenic?

BNC1 p.Arg24Trp (c.70C>T) is classified Uncertain significance in BNC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-18). AlphaMissense: likely benign (0.2918); Rare (popmax 0.173%, eas).

How common is BNC1 p.Arg24Trp (c.70C>T) in the general population?

BNC1 p.Arg24Trp (c.70C>T) is rare (popmax 0.173%, eas) (gnomAD).

What do computational predictors say about BNC1 p.Arg24Trp (c.70C>T)?

AlphaMissense predicts likely benign (score 0.2918) — an in-silico prediction, not a clinical call.

BNC1 p.Arg24Trp

c.70C>T · rs762547342 · VCV2365458

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2918 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.173%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2918	likely benign
REVEL	0.066	moderately benign-leaning
SaProt	LLR -9.10	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 -0.17	GERP -1.8
Regional constraint	o/e 0.96	unconstrained · MANE · 16 kb · p 0.75 · regional, not allelic
Overall
CADD	16.81	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 0.173% East Asian · 30/17,324 alleles

Filtering AF 0.125% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.108%

Overall 0.00317% 35/1,102,904 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.173%	577
Remaining individualsnot grpmax-eligible	0.00835%	11,973
Admixed American	0.00522%	19,172
European (non-Finnish)	0.00011%	906,084

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.Arg24Trp
Coding: c.70C>T
MANE Select: NM_001717
dbSNP: rs762547342
Type: single nucleotide variant
Location: chr15:83284559 (GRCh38)
Gene constraint: LOEUF 0.212 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.85
Residue 24: the 'disordered' region

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-arg24trp (accessed [today's date]).

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