Is PRIMA1 p.Asp147= (c.441C>T) pathogenic?

PRIMA1 p.Asp147= (c.441C>T) is classified Likely benign in PRIMA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-12). Very rare (popmax 0.00401%, afr); Associated with familial sleep-related hypermotor epilepsy.

What condition is associated with PRIMA1 p.Asp147= (c.441C>T)?

PRIMA1 p.Asp147= (c.441C>T) is associated with familial sleep-related hypermotor epilepsy (ClinVar).

How common is PRIMA1 p.Asp147= (c.441C>T) in the general population?

PRIMA1 p.Asp147= (c.441C>T) is very rare (popmax 0.00401%, afr) (gnomAD).

How is Sleep-related hypermotor epilepsy inherited?

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

PRIMA1 p.Asp147=

c.441C>T · rs966498472 · VCV2038635

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00401%, 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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -3.7	GERP -3.3
Overall
CADD	1.062	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00401% African / African-American · 3/74,900 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.00105% 17/1,612,998 alleles · very rare exomes 15/1,460,838 · genomes 2/152,160 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,967
East Asian	0.00223%	44,888
South Asian	0.0022%	45,529
European (non-Finnish)	0.000933%	107,199

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.Asp147=
Coding: c.441C>T
MANE Select: NM_178013
dbSNP: rs966498472
Type: single nucleotide variant
Location: chr14:93721465 (GRCh38)
Gene constraint: LOEUF 1.053 · pLI 0.07 (gnomAD)
Structure: AlphaFold pLDDT 63.74 · 1 PDB

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.Asp147Glu Uncertain significance ★ ⚠ same residue
PRIMA1 p.Asp147Gly 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

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-asp147 (accessed [today's date]).

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