Is CES2 p.Asp512Asn (c.1534G>A) pathogenic?

CES2 p.Asp512Asn (c.1534G>A) is classified Uncertain significance in CES2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-19). AlphaMissense: likely benign (0.0831); Ultra-rare (popmax 0.0201%, amr).

How common is CES2 p.Asp512Asn (c.1534G>A) in the general population?

CES2 p.Asp512Asn (c.1534G>A) is ultra-rare (popmax 0.0201%, amr) (gnomAD).

What do computational predictors say about CES2 p.Asp512Asn (c.1534G>A)?

AlphaMissense predicts likely benign (score 0.0831) — an in-silico prediction, not a clinical call.

CES2 p.Asp512Asn

c.1534G>A · rs140097117 · VCV3143235

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0831 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0201%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0831	likely benign
REVEL	0.057	moderately benign-leaning
SaProt	LLR -5.97	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.56 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.1	GERP 0.45
Overall
CADD	15.23	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 0.0201% Admixed American · 12/59,816 alleles

Filtering AF 0.0116% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00901%

Overall 0.00149% 24/1,606,752 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0201%	4,985
African / African-American	0.00401%	24,925
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,558
European (non-Finnish)	0.000681%	146,865

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: CES2
Protein: p.Asp512Asn
Coding: c.1534G>A
MANE Select: NM_001025195 · reported on NM_001365405
dbSNP: rs140097117
Type: single nucleotide variant
Location: chr16:66943879 (GRCh38)
Structure: AlphaFold pLDDT 93.27 · 21 PDB

Full CES2 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/ces2-p-asp512asn (accessed [today's date]).

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