Is CERS1 p.Ala8Val (c.23C>T) pathogenic?

CERS1 p.Ala8Val (c.23C>T) is classified Uncertain significance in CERS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-02). AlphaMissense: likely benign (0.1341); Absent from gnomAD v4.1.

How common is CERS1 p.Ala8Val (c.23C>T) in the general population?

CERS1 p.Ala8Val (c.23C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CERS1 p.Ala8Val (c.23C>T)?

AlphaMissense predicts likely benign (score 0.1341) — an in-silico prediction, not a clinical call.

CERS1 p.Ala8Val

c.23C>T · rs1568309719 · VCV3143152

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1341 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 985,946)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1341	likely benign
REVEL	0.06	moderately benign-leaning
SaProt	LLR -8.91	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 1.5	GERP -0.48, phastCons 0.022
Regional constraint	o/e 1.00	unconstrained · MANE · 25 kb · p 1 · regional, not allelic
Overall
CADD	15.55	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 985,946). 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.Ala8Val
Coding: c.23C>T
MANE Select: NM_021267
dbSNP: rs1568309719
Type: single nucleotide variant
Location: chr19:18896050 (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

Similar variants

CERS1 p.Ala8Gly Uncertain significance ★ ⚠ same residue
GDF1 p.Cys227Ter Pathogenic/Likely pathogenic ★★ same type
GDF1 p.Met364Thr Pathogenic/Likely pathogenic ★★ same type
CERS1 p.Ala117Ser Uncertain significance ★★ ⚠ same type
CERS1 p.Ala165Thr Uncertain significance ★★ ⚠ same type
CERS1 p.Ala266Val Uncertain significance ★★ ⚠ same type
CERS1 p.Ala286Val Uncertain significance ★★ ⚠ same type
CERS1 p.Ala304Val Uncertain significance ★★ ⚠ same type

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-ala8val (accessed [today's date]).

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