Is CES3 p.Phe438Ser (c.1313T>C) pathogenic?

CES3 p.Phe438Ser (c.1313T>C) is classified Uncertain significance in CES3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-05). AlphaMissense: ambiguous (0.5607); Absent from gnomAD v4.1.

How common is CES3 p.Phe438Ser (c.1313T>C) in the general population?

CES3 p.Phe438Ser (c.1313T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CES3 p.Phe438Ser (c.1313T>C)?

AlphaMissense predicts ambiguous (score 0.5607) — an in-silico prediction, not a clinical call.

CES3 p.Phe438Ser

c.1313T>C · VCV4226755

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5607 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.5607	ambiguous
REVEL	0.383	indeterminate
SaProt	LLR -10.47	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP 1.8, phastCons 0.082
Regional constraint	o/e 0.87	unconstrained · MANE · 12 kb · p 0.00037 · regional, not allelic
Overall
CADD	22.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CES3
Protein: p.Phe438Ser
Coding: c.1313T>C
MANE Select: NM_024922
Type: single nucleotide variant
Location: chr16:66972377 (GRCh38)
Gene constraint: LOEUF 0.987 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.89

Full CES3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CES3 p.Ala133Pro Uncertain significance ★ ⚠ same type
CES3 p.Ala137Thr Uncertain significance ★ ⚠ same type
CES3 p.Ala214Val Uncertain significance ★ ⚠ same type
CES3 p.Ala230Gly Uncertain significance ★ ⚠ same type
CES3 p.Ala244Thr Uncertain significance ★ ⚠ same type
CES3 p.Ala408Glu Uncertain significance ★ ⚠ same type
CES3 p.Ala449Glu Uncertain significance ★ ⚠ same type
CES3 p.Ala449Val 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/ces3-p-phe438ser (accessed [today's date]).

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