Is BNC2 p.Pro614Arg (c.1841C>G) pathogenic?

BNC2 p.Pro614Arg (c.1841C>G) is classified Uncertain significance in BNC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-01). AlphaMissense: likely benign (0.1428); Absent from gnomAD v4.1.

How common is BNC2 p.Pro614Arg (c.1841C>G) in the general population?

BNC2 p.Pro614Arg (c.1841C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BNC2 p.Pro614Arg (c.1841C>G)?

AlphaMissense predicts likely benign (score 0.1428) — an in-silico prediction, not a clinical call.

BNC2 p.Pro614Arg

c.1841C>G · VCV4702342

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1428 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1428	likely benign
REVEL	0.066	moderately benign-leaning
SaProt	LLR -8.53	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 0.94, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 18 kb · p 0.42 · regional, not allelic
Overall
CADD	23.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BNC2
Protein: p.Pro614Arg
Coding: c.1841C>G
MANE Select: NM_017637
Type: single nucleotide variant
Location: chr9:16436353 (GRCh38)
Gene constraint: LOEUF 0.365 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.10

Full BNC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BNC2 p.Ala386Val Uncertain significance ★★ ⚠ same type
BNC2 p.Arg536Gln Uncertain significance ★★ ⚠ same type
BNC2 p.Arg875His Uncertain significance ★★ ⚠ same type
BNC2 p.Asn1032Ser Uncertain significance ★★ ⚠ same type
BNC2 p.Asn1088Asp Uncertain significance ★★ ⚠ same type
BNC2 p.Asn668Ser Uncertain significance ★★ ⚠ same type
BNC2 p.Asn795Ser Uncertain significance ★★ ⚠ same type
BNC2 p.Asp690Glu 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/bnc2-p-pro614arg (accessed [today's date]).

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