Is PRIMA1 p.Pro63= (c.189G>A) pathogenic?

PRIMA1 p.Pro63= (c.189G>A) is classified Likely benign in PRIMA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-21). Rare (popmax 0.13%, sas); Associated with familial sleep-related hypermotor epilepsy.

What condition is associated with PRIMA1 p.Pro63= (c.189G>A)?

PRIMA1 p.Pro63= (c.189G>A) is associated with familial sleep-related hypermotor epilepsy (ClinVar).

How common is PRIMA1 p.Pro63= (c.189G>A) in the general population?

PRIMA1 p.Pro63= (c.189G>A) is rare (popmax 0.13%, sas) (gnomAD).

How is Sleep-related hypermotor epilepsy inherited?

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

PRIMA1 p.Pro63=

c.189G>A · rs775188425 · VCV1549193

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.13%, sas)

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	<0.2	all four deltas below 0.2 · C>G here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP -14	GERP -3.9
Overall
CADD	0.395	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.13% South Asian · 30/22,992 alleles

Filtering AF 0.0938% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0815%

Overall 0.0183% 76/415,192 alleles · rare exomes 71/403,278 · genomes 5/11,914 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.13%	766
Middle Eastern	0.0773%	1,294
African / African-American	0.0362%	2,759
Remaining individualsnot grpmax-eligible	0.0295%	3,388
European (non-Finnish)	0.0112%	8,927

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: PRIMA1
Protein: p.Pro63=
Coding: c.189G>A
MANE Select: NM_178013
dbSNP: rs775188425
Type: single nucleotide variant
Location: chr14:93779216 (GRCh38)
Gene constraint: LOEUF 1.053 · pLI 0.07 (gnomAD)
Structure: AlphaFold pLDDT 63.74 · 1 PDB
Residue 63: the prad domain; the 'disordered' region

Full PRIMA1 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

PRIMA1 p.Pro63Leu Uncertain significance ★ ⚠ same residue
PRIMA1 p.Arg55Trp Uncertain significance ★★ ⚠ same condition
PRIMA1 p.Asn79Ser Uncertain significance ★★ ⚠ same condition
PRIMA1 p.Gly145Arg Uncertain significance ★★ ⚠ same condition
PRIMA1 p.Ile118Thr Uncertain significance ★★ ⚠ same condition
PRIMA1 p.Leu6Val Uncertain significance ★★ ⚠ same condition
PRIMA1 p.Pro59Leu Uncertain significance ★★ ⚠ same condition
PRIMA1 p.Pro84Ala 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/prima1-p-pro63 (accessed [today's date]).

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