Is BNC2 p.Pro568Ser (c.1702C>T) pathogenic?

BNC2 p.Pro568Ser (c.1702C>T) is classified Uncertain significance in BNC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-01). AlphaMissense: ambiguous (0.5502); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with BNC2 p.Pro568Ser (c.1702C>T)?

BNC2 p.Pro568Ser (c.1702C>T) is associated with Inborn genetic diseases (ClinVar).

How common is BNC2 p.Pro568Ser (c.1702C>T) in the general population?

BNC2 p.Pro568Ser (c.1702C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about BNC2 p.Pro568Ser (c.1702C>T)?

AlphaMissense predicts ambiguous (score 0.5502) — an in-silico prediction, not a clinical call.

BNC2 p.Pro568Ser

c.1702C>T · VCV4214642

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5502 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5502	ambiguous
REVEL	0.311	indeterminate
SaProt	LLR -6.33	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 18 kb · p 0.42 · regional, not allelic
Overall
CADD	25.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,992 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,613,984 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,992
European (non-Finnish)	0.000254%	393,345

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: BNC2
Protein: p.Pro568Ser
Coding: c.1702C>T
MANE Select: NM_017637
Type: single nucleotide variant
Location: chr9:16436492 (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-pro568ser (accessed [today's date]).

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