Is CERS1 p.Arg228= (c.684C>T) pathogenic?

CERS1 p.Arg228= (c.684C>T) is classified Likely benign in CERS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-04-25). Very rare (popmax 0.0024%, eas); Associated with progressive myoclonic epilepsy type 8.

What condition is associated with CERS1 p.Arg228= (c.684C>T)?

CERS1 p.Arg228= (c.684C>T) is associated with progressive myoclonic epilepsy type 8 (ClinVar).

How common is CERS1 p.Arg228= (c.684C>T) in the general population?

CERS1 p.Arg228= (c.684C>T) is very rare (popmax 0.0024%, eas) (gnomAD).

How is Progressive myoclonic epilepsy type 8 inherited?

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

CERS1 p.Arg228=

c.684C>T · rs761091051 · VCV1084205

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0024%, eas)

Conditions

progressive myoclonic epilepsy type 8

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 -4.9	GERP -2
Overall
CADD	4.515	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0024% East Asian · 1/41,622 alleles

Overall 0.000192% 3/1,558,720 alleles · very rare exomes 2/1,406,550 · genomes 1/152,170 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0024%	41,622
Remaining individualsnot grpmax-eligible	0.00166%	60,396
African / African-American	0.00136%	73,388

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: CERS1
Protein: p.Arg228=
Coding: c.684C>T
MANE Select: NM_021267
dbSNP: rs761091051
Type: single nucleotide variant
Location: chr19:18880342 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 88.95
Residue 228: a UniProt-annotated variant site (in epm8); the tlc domain

Full CERS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

progressive myoclonic epilepsy type 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Progressive myoclonic epilepsy type 8 (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Childhood

Similar variants

CERS1 p.Arg228Cys Uncertain significance ★★ ⚠ same residue
CERS1 p.Arg228His Uncertain significance ★ ⚠ same residue
GDF1 p.Ala228Thr Uncertain significance ★ ⚠ same residue
CERS1 p.Ala117Ser Uncertain significance ★★ ⚠ same condition
CERS1 p.Ala165Thr Uncertain significance ★★ ⚠ same condition
CERS1 p.Ala266Val Uncertain significance ★★ ⚠ same condition
CERS1 p.Ala286Val Uncertain significance ★★ ⚠ same condition
CERS1 p.Ala304Val 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/cers1-p-arg228 (accessed [today's date]).

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