Is CERS1 p.Leu204Val (c.610C>G) pathogenic?

CERS1 p.Leu204Val (c.610C>G) is classified Uncertain significance in CERS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-01). AlphaMissense: ambiguous (0.3571); Very rare (popmax 0.00114%, sas); Associated with progressive myoclonic epilepsy type 8.

What condition is associated with CERS1 p.Leu204Val (c.610C>G)?

CERS1 p.Leu204Val (c.610C>G) is associated with progressive myoclonic epilepsy type 8 (ClinVar).

How common is CERS1 p.Leu204Val (c.610C>G) in the general population?

CERS1 p.Leu204Val (c.610C>G) is very rare (popmax 0.00114%, sas) (gnomAD).

How is Progressive myoclonic epilepsy type 8 inherited?

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

What do computational predictors say about CERS1 p.Leu204Val (c.610C>G)?

AlphaMissense predicts ambiguous (score 0.3571) — an in-silico prediction, not a clinical call.

CERS1 p.Leu204Val

c.610C>G · rs866186539 · VCV1038481

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3571 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00114%, sas)

Conditions

progressive myoclonic epilepsy type 8

Computational evidence

Protein change
AlphaMissense	0.3571	ambiguous
REVEL	0.634	indeterminate
SaProt	LLR -6.79	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 1, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 25 kb · p 1 · regional, not allelic
Overall
CADD	25.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00114% South Asian · 1/87,370 alleles

Filtering AF 0.000126% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.1e-05%

Overall 0.000418% 6/1,437,078 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00114%	87,370
European (non-Finnish)	0.000428%	233,421

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.Leu204Val
Coding: c.610C>G
MANE Select: NM_021267
dbSNP: rs866186539
Type: single nucleotide variant
Location: chr19:18880416 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 88.95
Residue 204: 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.Leu204= Likely benign ★ same residue
CERS1 p.Leu204His 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-leu204val (accessed [today's date]).

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