Is CERS1 p.Pro6Thr (c.16C>A) pathogenic?

CERS1 p.Pro6Thr (c.16C>A) is classified Conflicting classifications of pathogenicity in CERS1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.0734); Rare (popmax 0.247%, afr); Associated with progressive myoclonic epilepsy type 8.

What condition is associated with CERS1 p.Pro6Thr (c.16C>A)?

CERS1 p.Pro6Thr (c.16C>A) is associated with progressive myoclonic epilepsy type 8 (ClinVar).

How common is CERS1 p.Pro6Thr (c.16C>A) in the general population?

CERS1 p.Pro6Thr (c.16C>A) is rare (popmax 0.247%, afr) (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.Pro6Thr (c.16C>A)?

AlphaMissense predicts likely benign (score 0.0734) — an in-silico prediction, not a clinical call.

CERS1 p.Pro6Thr

c.16C>A · rs1041161328 · VCV542128

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0734 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.247%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

progressive myoclonic epilepsy type 8

Computational evidence

Protein change
AlphaMissense	0.0734	likely benign
REVEL	0.016	strongly benign-leaning
SaProt	LLR -8.17	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 -2.8	GERP -1.4
Regional constraint	o/e 1.00	unconstrained · MANE · 25 kb · p 1 · regional, not allelic
Overall
CADD	0.482	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 0.247% African / African-American · 140/56,696 alleles

Filtering AF 0.214% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.201%

Overall 0.0146% 143/982,440 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.247%	405
Remaining individualsnot grpmax-eligible	0.00677%	14,773
Admixed American	0.00628%	15,914

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.Pro6Thr
Coding: c.16C>A
MANE Select: NM_021267
dbSNP: rs1041161328
Type: single nucleotide variant
Location: chr19:18896057 (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.Pro6Arg Uncertain significance ★ ⚠ same residue
CERS1 p.Pro6= 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
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-pro6thr (accessed [today's date]).

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