Is CERS1 p.His183= (c.549C>T) pathogenic?

CERS1 p.His183= (c.549C>T) is classified Likely benign in CERS1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-15). Ultra-rare (popmax 0.033%, mid); Associated with progressive myoclonic epilepsy type 8.

What condition is associated with CERS1 p.His183= (c.549C>T)?

CERS1 p.His183= (c.549C>T) is associated with progressive myoclonic epilepsy type 8 (ClinVar).

How common is CERS1 p.His183= (c.549C>T) in the general population?

CERS1 p.His183= (c.549C>T) is ultra-rare (popmax 0.033%, mid) (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.His183=

c.549C>T · rs200024180 · VCV1674175

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

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 -6.4	GERP -1.2
Overall
CADD	1.256	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.0144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0118%

Overall 0.00428% 69/1,613,558 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,031
African / African-American	0.0227%	4,412
South Asian	0.0209%	4,789
Remaining individualsnot grpmax-eligible	0.0048%	20,823
European (non-Finnish)	0.00237%	42,135

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.His183=
Coding: c.549C>T
MANE Select: NM_021267
dbSNP: rs200024180
Type: single nucleotide variant
Location: chr19:18884128 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 88.95
Residue 183: a UniProt-annotated variant site (in epm8); a UniProt-annotated variant site (in epm8; expressed and localized properly to the er; impaired ceramide synthase activity); 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.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
CERS1 p.Ala45Pro Uncertain significance ★★ ⚠ same condition
CERS1 p.Ala86Val Uncertain significance ★★ ⚠ same condition
CERS1 p.Ala97Thr 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-his183 (accessed [today's date]).

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