Is CERS1 p.Ala50Ser (c.148G>T) pathogenic?

CERS1 p.Ala50Ser (c.148G>T) is classified Uncertain significance in CERS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-08). AlphaMissense: likely benign (0.103); Absent from gnomAD v4.1; Associated with progressive myoclonic epilepsy type 8.

What condition is associated with CERS1 p.Ala50Ser (c.148G>T)?

CERS1 p.Ala50Ser (c.148G>T) is associated with progressive myoclonic epilepsy type 8 (ClinVar).

How common is CERS1 p.Ala50Ser (c.148G>T) in the general population?

CERS1 p.Ala50Ser (c.148G>T) is absent from gnomAD v4.1 (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.Ala50Ser (c.148G>T)?

AlphaMissense predicts likely benign (score 0.103) — an in-silico prediction, not a clinical call.

CERS1 p.Ala50Ser

c.148G>T · rs948253146 · VCV2022792

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.103 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,217,886)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

progressive myoclonic epilepsy type 8

Computational evidence

Protein change
AlphaMissense	0.103	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -8.47	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP -0.49, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 25 kb · p 1 · regional, not allelic
Overall
CADD	18.31	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,217,886). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CERS1
Protein: p.Ala50Ser
Coding: c.148G>T
MANE Select: NM_021267
dbSNP: rs948253146
Type: single nucleotide variant
Location: chr19:18895925 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 88.95

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.Ala50Pro Uncertain significance ★ ⚠ same residue
GDF1 p.Gln50Ter Likely pathogenic ★ same residue
GDF1 p.Gln50Arg Likely benign ★ 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-ala50ser (accessed [today's date]).

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