Is BNC2 p.Pro623His (c.1868C>A) pathogenic?

BNC2 p.Pro623His (c.1868C>A) is classified Benign/Likely benign in BNC2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-26). AlphaMissense: likely benign (0.0856); Low-frequency (popmax 1.1%, afr); Associated with hypotensive disorder.

What condition is associated with BNC2 p.Pro623His (c.1868C>A)?

BNC2 p.Pro623His (c.1868C>A) is associated with hypotensive disorder (ClinVar).

How common is BNC2 p.Pro623His (c.1868C>A) in the general population?

BNC2 p.Pro623His (c.1868C>A) is low-frequency (popmax 1.1%, afr) (gnomAD).

What do computational predictors say about BNC2 p.Pro623His (c.1868C>A)?

AlphaMissense predicts likely benign (score 0.0856) — an in-silico prediction, not a clinical call.

BNC2 p.Pro623His

c.1868C>A · rs114596065 · VCV120232

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0856 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.1%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hypotensive disorder

Computational evidence

Protein change
AlphaMissense	0.0856	likely benign
REVEL	0.114	moderately benign-leaning
SaProt	LLR -7.50	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 10	GERP 1.9, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 18 kb · p 0.42 · regional, not allelic
Overall
CADD	23.5	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 1.1% African / African-American · 825/75,016 alleles

Filtering AF 1.04% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.01%

Overall 0.181% 2,928/1,614,108 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.1%	91
Middle Eastern	0.759%	132
Remaining individualsnot grpmax-eligible	0.253%	396
Admixed American	0.182%	551
European (non-Finnish)	0.148%	677
Ashkenazi Jewishnot grpmax-eligible	0.0439%	2,277
Finnishnot grpmax-eligible	0.0406%	2,462
South Asian	0.00659%	15,178
East Asian	0.00223%	44,876

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.Pro623His
Coding: c.1868C>A
MANE Select: NM_017637
dbSNP: rs114596065
Type: single nucleotide variant
Location: chr9:16436326 (GRCh38)
Gene constraint: LOEUF 0.365 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.10
Residue 623: the 'disordered' region

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

Disease context

hypotensive disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BNC2 p.Ala28= Benign ★★ same condition
BNC2 p.Ala923Val Benign/Likely benign ★★ same condition
BNC2 p.Asp930Gly Likely benign ★★ same condition
BNC2 p.Ile974Val Benign ★★ same condition
BNC2 p.Leu414Val Benign ★★ same condition
BNC2 p.Leu826= Benign/Likely benign ★★ same condition
BNC2 p.Phe312= Benign ★★ same condition
BNC2 p.Ser173= Benign/Likely benign ★★ 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-pro623his (accessed [today's date]).

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