Is CHRNB4 p.Pro481= (c.1443C>A) pathogenic?

CHRNB4 p.Pro481= (c.1443C>A) is classified Likely benign in CHRNB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-08-03). Very rare (popmax 0.00755%, nfe).

How common is CHRNB4 p.Pro481= (c.1443C>A) in the general population?

CHRNB4 p.Pro481= (c.1443C>A) is very rare (popmax 0.00755%, nfe) (gnomAD).

CHRNB4 p.Pro481=

c.1443C>A · rs571462279 · VCV762453

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00755%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.155	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.76	GERP -0.34, phastCons 1
Overall
CADD	6.66	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00755% European (non-Finnish) · 89/1,178,956 alleles

Filtering AF 0.00623% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00579%

Overall 0.00552% 89/1,611,508 alleles · very rare

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: CHRNB4
Protein: p.Pro481=
Coding: c.1443C>A
MANE Select: NM_000750
dbSNP: rs571462279
Type: single nucleotide variant
Location: chr15:78625187 (GRCh38)
Gene constraint: LOEUF 0.772 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.08 · 4 PDB

Full CHRNB4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHRNB4 c.*76T>C Benign ★★ same type
CHRNB4 p.Asn41Ser Benign ★★ ⚠ same type
CHRNB4 p.Ile240= Benign ★★ same type
CHRNB4 p.Thr375Ile Benign ★★ ⚠ same type
CHRNB4 p.Ala14Asp Uncertain significance ★ ⚠ same type
CHRNB4 p.Ala14Val Uncertain significance ★ ⚠ same type
CHRNB4 p.Ala393Thr Uncertain significance ★ ⚠ same type
CHRNB4 p.Ala395Thr 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/chrnb4-p-pro481 (accessed [today's date]).

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