Is CES5A p.Phe348Ser (c.1043T>C) pathogenic?

CES5A p.Phe348Ser (c.1043T>C) is classified Uncertain significance in CES5A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-01). AlphaMissense: likely pathogenic (0.5868); Rare (popmax 0.125%, mid).

How common is CES5A p.Phe348Ser (c.1043T>C) in the general population?

CES5A p.Phe348Ser (c.1043T>C) is rare (popmax 0.125%, mid) (gnomAD).

What do computational predictors say about CES5A p.Phe348Ser (c.1043T>C)?

AlphaMissense predicts likely pathogenic (score 0.5868) — an in-silico prediction, not a clinical call.

CES5A p.Phe348Ser

c.1043T>C · rs202084980 · VCV3143260

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5868 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.125%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.5868	likely pathogenic
REVEL	0.321	indeterminate
SaProt	LLR -7.26	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.47	GERP -3.8, phastCons 0.067
Regional constraint	o/e 1.06	unconstrained · MANE · 29 kb · p 0.14 · regional, not allelic
Overall
CADD	18.97	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 0.125% Middle Eastern · 7/5,600 alleles

Filtering AF 0.0586% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0416%

Overall 0.00453% 73/1,612,536 alleles · rare exomes 70/1,460,304 · genomes 3/152,232 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.125%	800
Ashkenazi Jewishnot grpmax-eligible	0.0237%	4,226
Remaining individualsnot grpmax-eligible	0.0192%	5,199
Admixed American	0.0117%	8,541
European (non-Finnish)	0.00314%	31,887
African / African-American	0.00267%	37,439
South Asian	0.0011%	90,670

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: CES5A
Protein: p.Phe348Ser
Coding: c.1043T>C
MANE Select: NM_001143685
dbSNP: rs202084980
Type: single nucleotide variant
Location: chr16:55859560 (GRCh38)
Gene constraint: LOEUF 1.26 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.48

Full CES5A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CES5A p.Leu527= Benign ★★ same type
CES5A p.Ala154Gly Uncertain significance ★ ⚠ same type
CES5A p.Ala195Val Uncertain significance ★ ⚠ same type
CES5A p.Ala262Thr Uncertain significance ★ ⚠ same type
CES5A p.Ala282Val Uncertain significance ★ ⚠ same type
CES5A p.Ala334Thr Uncertain significance ★ ⚠ same type
CES5A p.Ala465Gly Uncertain significance ★ ⚠ same type
CES5A p.Ala465Pro 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/ces5a-p-phe348ser (accessed [today's date]).

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