Is CES5A p.Ala282Val (c.845C>T) pathogenic?

CES5A p.Ala282Val (c.845C>T) is classified Uncertain significance in CES5A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-28). AlphaMissense: likely benign (0.092); Very rare (popmax 0.00267%, afr).

How common is CES5A p.Ala282Val (c.845C>T) in the general population?

CES5A p.Ala282Val (c.845C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about CES5A p.Ala282Val (c.845C>T)?

AlphaMissense predicts likely benign (score 0.092) — an in-silico prediction, not a clinical call.

CES5A p.Ala282Val

c.845C>T · rs771701068 · VCV2552450

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.092 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.092	likely benign
REVEL	0.171	moderately benign-leaning
SaProt	LLR -6.86	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 -1.2	GERP -3.4
Regional constraint	o/e 1.06	unconstrained · MANE · 29 kb · p 0.14 · regional, not allelic
Overall
CADD	0.128	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,916 alleles

Filtering AF 0.00153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0013%

Overall 0.00186% 30/1,613,488 alleles · very rare exomes 27/1,461,304 · genomes 3/152,184 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,458
East Asian	0.00223%	44,882
European (non-Finnish)	0.0022%	45,367
Admixed American	0.00167%	59,996

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.Ala282Val
Coding: c.845C>T
MANE Select: NM_001143685
dbSNP: rs771701068
Type: single nucleotide variant
Location: chr16:55861482 (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.Ala334Thr Uncertain significance ★ ⚠ same type
CES5A p.Ala465Gly Uncertain significance ★ ⚠ same type
CES5A p.Ala465Pro Uncertain significance ★ ⚠ same type
CES5A p.Arg293Gly 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-ala282val (accessed [today's date]).

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