Is BNC2 p.Pro8Ser (c.22C>T) pathogenic?

BNC2 p.Pro8Ser (c.22C>T) is classified Uncertain significance in BNC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-19). AlphaMissense: likely benign (0.07); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with BNC2 p.Pro8Ser (c.22C>T)?

BNC2 p.Pro8Ser (c.22C>T) is associated with Inborn genetic diseases (ClinVar).

How common is BNC2 p.Pro8Ser (c.22C>T) in the general population?

BNC2 p.Pro8Ser (c.22C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BNC2 p.Pro8Ser (c.22C>T)?

AlphaMissense predicts likely benign (score 0.07) — an in-silico prediction, not a clinical call.

BNC2 p.Pro8Ser

c.22C>T · VCV3261278

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.07 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.07	likely benign
REVEL	0.062	moderately benign-leaning
SaProt	LLR -6.05	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 0.73	GERP -0.79, phastCons 0.001
Regional constraint	o/e 1.03	unconstrained · MANE · 434 kb · p 0.49 · regional, not allelic
Overall
CADD	6.126	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.Pro8Ser
Coding: c.22C>T
MANE Select: NM_017637
Type: single nucleotide variant
Location: chr9:16738467 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BNC2 p.Ala386Val Uncertain significance ★★ ⚠ same condition
BNC2 p.Arg536Gln Uncertain significance ★★ ⚠ same condition
BNC2 p.Arg875His Uncertain significance ★★ ⚠ same condition
BNC2 p.Asn1088Asp Uncertain significance ★★ ⚠ same condition
BNC2 p.Asn668Ser Uncertain significance ★★ ⚠ same condition
BNC2 p.Asn795Ser Uncertain significance ★★ ⚠ same condition
BNC2 p.Asp690Glu Uncertain significance ★★ ⚠ same condition
BNC2 p.Asp741Glu Uncertain significance ★★ ⚠ same condition

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-pro8ser (accessed [today's date]).

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