Is PRICKLE1 p.Ser549= (c.1647G>A) pathogenic?

PRICKLE1 p.Ser549= (c.1647G>A) is classified Benign/Likely benign in PRICKLE1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-16). Ultra-rare (popmax 0.0269%, nfe); Associated with epilepsy, progressive myoclonic, 1B.

What condition is associated with PRICKLE1 p.Ser549= (c.1647G>A)?

PRICKLE1 p.Ser549= (c.1647G>A) is associated with epilepsy, progressive myoclonic, 1B (ClinVar).

How common is PRICKLE1 p.Ser549= (c.1647G>A) in the general population?

PRICKLE1 p.Ser549= (c.1647G>A) is ultra-rare (popmax 0.0269%, nfe) (gnomAD).

PRICKLE1 p.Ser549=

c.1647G>A · rs149518219 · VCV378424

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0269%, nfe)

Conditions

epilepsy, progressive myoclonic, 1B

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 -3.5
Overall
CADD	0.006	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0269% European (non-Finnish) · 318/1,179,996 alleles

Filtering AF 0.0245% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0235%

Overall 0.0204% 328/1,608,672 alleles · ultra-rare exomes 312/1,456,548 · genomes 16/152,124 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0269%	3,711
Remaining individualsnot grpmax-eligible	0.00801%	12,490
African / African-American	0.00401%	24,965
Finnishnot grpmax-eligible	0.0017%	58,770
Admixed American	0.00167%	59,992

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: PRICKLE1
Protein: p.Ser549=
Coding: c.1647G>A
MANE Select: NM_153026
dbSNP: rs149518219
Type: single nucleotide variant
Location: chr12:42460658 (GRCh38)
Gene constraint: LOEUF 0.279 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 55.55

Full PRICKLE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

epilepsy, progressive myoclonic, 1B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRICKLE1 p.Ser549Leu Uncertain significance ★★ same residue
PRICKLE1 c.1639+4C>T Uncertain significance ★★ same condition
PRICKLE1 c.384+6C>A Uncertain significance ★★ same condition
PRICKLE1 p.Ala142Thr Uncertain significance ★★ ⚠ same condition
PRICKLE1 p.Ala145Val Uncertain significance ★★ ⚠ same condition
PRICKLE1 p.Ala34Thr Uncertain significance ★★ ⚠ same condition
PRICKLE1 p.Ala34Val Uncertain significance ★★ ⚠ same condition
PRICKLE1 p.Ala492Thr 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/prickle1-p-ser549 (accessed [today's date]).

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