Is CERS1 p.Arg173= (c.519C>A) pathogenic?

CERS1 p.Arg173= (c.519C>A) is classified Likely benign in CERS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-28). Ultra-rare (popmax 0.0165%, mid); Associated with progressive myoclonic epilepsy type 8.

What condition is associated with CERS1 p.Arg173= (c.519C>A)?

CERS1 p.Arg173= (c.519C>A) is associated with progressive myoclonic epilepsy type 8 (ClinVar).

How common is CERS1 p.Arg173= (c.519C>A) in the general population?

CERS1 p.Arg173= (c.519C>A) is ultra-rare (popmax 0.0165%, 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.Arg173=

c.519C>A · rs575712132 · VCV1147889

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, 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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.2	GERP 0.075, phastCons 1
Overall
CADD	6.648	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.0121% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0115%

Overall 0.0108% 175/1,613,790 alleles · ultra-rare exomes 156/1,461,516 · genomes 19/152,274 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
European (non-Finnish)	0.0139%	7,194
Remaining individualsnot grpmax-eligible	0.0128%	7,810
African / African-American	0.00267%	37,520

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.Arg173=
Coding: c.519C>A
MANE Select: NM_021267
dbSNP: rs575712132
Type: single nucleotide variant
Location: chr19:18884158 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 88.95
Residue 173: 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.Arg173His Uncertain significance ★ ⚠ same residue
GDF1 p.Gly173Ser 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
CERS1 p.Ala45Pro 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-arg173 (accessed [today's date]).

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