Is CES5A p.Val173Phe (c.517G>T) pathogenic?

CES5A p.Val173Phe (c.517G>T) is classified Uncertain significance in CES5A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-28). AlphaMissense: likely benign (0.2762); Very rare (popmax 0.00932%, nfe).

How common is CES5A p.Val173Phe (c.517G>T) in the general population?

CES5A p.Val173Phe (c.517G>T) is very rare (popmax 0.00932%, nfe) (gnomAD).

What do computational predictors say about CES5A p.Val173Phe (c.517G>T)?

AlphaMissense predicts likely benign (score 0.2762) — an in-silico prediction, not a clinical call.

CES5A p.Val173Phe

c.517G>T · VCV4226782

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2762 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00932%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2762	likely benign
REVEL	0.102	moderately benign-leaning
SaProt	LLR -10.65	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 0.13	GERP -3.8
Regional constraint	o/e 1.06	unconstrained · MANE · 29 kb · p 0.14 · regional, not allelic
Overall
CADD	2.924	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 0.00932% European (non-Finnish) · 110/1,179,930 alleles

Filtering AF 0.00791% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00736%

Overall 0.00694% 112/1,613,670 alleles · very rare exomes 108/1,461,612 · genomes 4/152,058 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00932%	10,727
Remaining individualsnot grpmax-eligible	0.0032%	31,234

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.Val173Phe
Coding: c.517G>T
MANE Select: NM_001143685
Type: single nucleotide variant
Location: chr16:55869645 (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-val173phe (accessed [today's date]).

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