Is CHRNA4 p.Pro620= (c.1860G>A) pathogenic?

CHRNA4 p.Pro620= (c.1860G>A) is classified Likely benign in CHRNA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-22). Very rare (popmax 0.004%, afr); Associated with familial sleep-related hypermotor epilepsy.

What condition is associated with CHRNA4 p.Pro620= (c.1860G>A)?

CHRNA4 p.Pro620= (c.1860G>A) is associated with familial sleep-related hypermotor epilepsy (ClinVar).

How common is CHRNA4 p.Pro620= (c.1860G>A) in the general population?

CHRNA4 p.Pro620= (c.1860G>A) is very rare (popmax 0.004%, afr) (gnomAD).

How is Sleep-related hypermotor epilepsy inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

CHRNA4 p.Pro620=

c.1860G>A · rs202203317 · VCV416914

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Conditions

familial sleep-related hypermotor epilepsy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -13
Overall
CADD	1.522	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/75,022 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.0018% 29/1,611,158 alleles · very rare exomes 27/1,458,846 · genomes 2/152,312 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	25,007
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,584
East Asian	0.00223%	44,854
South Asian	0.0022%	45,530
European (non-Finnish)	0.00186%	53,619

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: CHRNA4
Protein: p.Pro620=
Coding: c.1860G>A
MANE Select: NM_000744
dbSNP: rs202203317
Type: single nucleotide variant
Location: chr20:63346762 (GRCh38)
Gene constraint: LOEUF 0.834 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 73.42 · 12 PDB
Residue 620: an α-helix

Full CHRNA4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

familial sleep-related hypermotor epilepsy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Sleep-related hypermotor epilepsy (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

CHRNA4 p.Pro620Leu Uncertain significance ★★ ⚠ same residue
CHRNA4 p.Pro620Arg Uncertain significance ★ ⚠ same residue
CHRNA4 p.Pro620Ser Uncertain significance ★ ⚠ same residue
CHRNA4 p.Ile275Phe Likely pathogenic ★★ same condition
CHRNA4 p.Ser280Phe Pathogenic ★★ same condition
CHRNA4 p.Ser284Leu Pathogenic ★★ same condition
CHRNA4 c.274-1G>A Uncertain significance ★★ same condition
CHRNA4 c.383+1G>A 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/chrna4-p-pro620 (accessed [today's date]).

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