Is CERS1 p.Pro84Thr (c.250C>A) pathogenic?

CERS1 p.Pro84Thr (c.250C>A) is classified Uncertain significance in CERS1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-08-19). AlphaMissense: ambiguous (0.5162); Ultra-rare (popmax 0.0171%, mid); Associated with progressive myoclonic epilepsy type 8.

What condition is associated with CERS1 p.Pro84Thr (c.250C>A)?

CERS1 p.Pro84Thr (c.250C>A) is associated with progressive myoclonic epilepsy type 8 (ClinVar).

How common is CERS1 p.Pro84Thr (c.250C>A) in the general population?

CERS1 p.Pro84Thr (c.250C>A) is ultra-rare (popmax 0.0171%, mid) (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.Pro84Thr (c.250C>A)?

AlphaMissense predicts ambiguous (score 0.5162) — an in-silico prediction, not a clinical call.

CERS1 p.Pro84Thr

c.250C>A · rs755371379 · VCV643935

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.5162 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0171%, mid)

Conditions

progressive myoclonic epilepsy type 8

Computational evidence

Protein change
AlphaMissense	0.5162	ambiguous
REVEL	0.429	indeterminate
SaProt	LLR -14.72	damaging
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 25 kb · p 1 · regional, not allelic
Overall
CADD	26.0	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 0.0171% Middle Eastern · 1/5,864 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000747% 12/1,606,838 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0171%	5,864
Admixed American	0.00169%	59,106
European (non-Finnish)	0.000849%	117,762

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.Pro84Thr
Coding: c.250C>A
MANE Select: NM_001492 · reported on NM_021267
dbSNP: rs755371379
Type: single nucleotide variant
Location: chr19:18893575 (GRCh38)

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

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-pro84thr (accessed [today's date]).

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