Is CES1 p.Pro47Ser (c.139C>T) pathogenic?

CES1 p.Pro47Ser (c.139C>T) is classified Uncertain significance in CES1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-16). AlphaMissense: likely benign (0.1483); Ultra-rare (popmax 0.0165%, mid).

How common is CES1 p.Pro47Ser (c.139C>T) in the general population?

CES1 p.Pro47Ser (c.139C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CES1 p.Pro47Ser (c.139C>T)?

AlphaMissense predicts likely benign (score 0.1483) — an in-silico prediction, not a clinical call.

CES1 p.Pro47Ser

c.139C>T · rs751739988 · VCV2307106

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1483 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1483	likely benign
REVEL	0.145	moderately benign-leaning
SaProt	LLR -11.22	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	GERP 1.8, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 6,902 bp · p 0.9 · regional, not allelic
Overall
CADD	21.6	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P46S vs ClinVar P47S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.00174% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000342% 5/1,461,806 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
African / African-American	0.00533%	18,772

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.Pro47Ser
Coding: c.139C>T
MANE Select: NM_001025195
dbSNP: rs751739988
Type: single nucleotide variant
Location: chr16:55828888 (GRCh38)
Gene constraint: LOEUF 1.272 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.27 · 21 PDB
Residue 47: a β-strand

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

Similar variants

CES1 p.Val166Met Uncertain significance ★★ ⚠ same type
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
CES1 p.Ala338Gly 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-pro47ser (accessed [today's date]).

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