Is CES1 p.His161Arg (c.482A>G) pathogenic?

CES1 p.His161Arg (c.482A>G) is classified Uncertain significance in CES1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-25). AlphaMissense: likely benign (0.0885); Very rare (popmax 0.00667%, amr).

How common is CES1 p.His161Arg (c.482A>G) in the general population?

CES1 p.His161Arg (c.482A>G) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about CES1 p.His161Arg (c.482A>G)?

AlphaMissense predicts likely benign (score 0.0885) — an in-silico prediction, not a clinical call.

CES1 p.His161Arg

c.482A>G · VCV3832180

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0885 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0885	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -7.33	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 -0.039	GERP -0.5
Regional constraint	o/e 0.08	constrained · MANE · 2,576 bp · p 7.7e-11 · regional, not allelic
Overall
CADD	18.81	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM H160R vs ClinVar H161R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% Admixed American · 4/59,988 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000744% 12/1,613,666 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	14,997
African / African-American	0.00134%	74,698
European (non-Finnish)	0.000593%	168,558

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.His161Arg
Coding: c.482A>G
MANE Select: NM_001025195
Type: single nucleotide variant
Location: chr16:55823607 (GRCh38)
Gene constraint: LOEUF 1.272 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.27 · 21 PDB
Residue 161: an α-helix

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-his161arg (accessed [today's date]).

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