Is CES1 p.Ala45Val (c.134C>T) pathogenic?

CES1 p.Ala45Val (c.134C>T) is classified Uncertain significance in CES1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-30). AlphaMissense: likely benign (0.0993); Rare (popmax 0.412%, mid); Associated with CES1-related condition.

What condition is associated with CES1 p.Ala45Val (c.134C>T)?

CES1 p.Ala45Val (c.134C>T) is associated with CES1-related condition (ClinVar).

How common is CES1 p.Ala45Val (c.134C>T) in the general population?

CES1 p.Ala45Val (c.134C>T) is rare (popmax 0.412%, mid) (gnomAD).

What do computational predictors say about CES1 p.Ala45Val (c.134C>T)?

AlphaMissense predicts likely benign (score 0.0993) — an in-silico prediction, not a clinical call.

CES1 p.Ala45Val

c.134C>T · VCV3779054

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0993 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.412%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CES1-related condition

Computational evidence

Protein change
AlphaMissense	0.0993	likely benign
REVEL	0.106	moderately benign-leaning
SaProt	LLR -3.65	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 0.48	GERP 0.83
Regional constraint	o/e 1.01	unconstrained · MANE · 6,902 bp · p 0.9 · regional, not allelic
Overall
CADD	15.48	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A44V vs ClinVar A45V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.412% Middle Eastern · 25/6,062 alleles

Filtering AF 0.287% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.245%

Overall 0.0156% 252/1,614,202 alleles · rare exomes 237/1,461,794 · genomes 15/152,408 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.412%	242
Remaining individualsnot grpmax-eligible	0.0192%	5,209
European (non-Finnish)	0.0166%	6,021
South Asian	0.0154%	6,503
Admixed American	0.005%	20,012
Finnishnot grpmax-eligible	0.00156%	64,048
African / African-American	0.00133%	75,076

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: CES1
Protein: p.Ala45Val
Coding: c.134C>T
MANE Select: NM_001025195
Type: single nucleotide variant
Location: chr16:55828893 (GRCh38)
Gene constraint: LOEUF 1.272 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.27 · 21 PDB

Full CES1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CES1-related condition

Similar variants

CES1 p.Ala45= Likely benign ★ same residue
CES1 p.Val166Met Uncertain significance ★★ ⚠ same condition
CES2 p.Glu366= Benign ★★ same type
CES1 p.Ala126Asp Uncertain significance ★ ⚠ same type
CES1 p.Ala126Val Uncertain significance ★ ⚠ same type
CES1 p.Ala149Glu Uncertain significance ★ ⚠ same type
CES1 p.Ala160Thr Uncertain significance ★ ⚠ same type
CES1 p.Ala197Asp 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/ces1-p-ala45val (accessed [today's date]).

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