Is CES4A p.Cys515Arg (c.1543T>C) pathogenic?

CES4A p.Cys515Arg (c.1543T>C) is classified Likely benign in CES4A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-24). AlphaMissense: likely benign (0.086); Absent from gnomAD v4.1.

How common is CES4A p.Cys515Arg (c.1543T>C) in the general population?

CES4A p.Cys515Arg (c.1543T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CES4A p.Cys515Arg (c.1543T>C)?

AlphaMissense predicts likely benign (score 0.086) — an in-silico prediction, not a clinical call.

CES4A p.Cys515Arg

c.1543T>C · VCV4652701

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.086 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.086	likely benign
REVEL	0.108	moderately benign-leaning
SaProt	LLR -2.66	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 -0.93	GERP -4
Regional constraint	o/e 0.94	unconstrained · MANE · 20 kb · p 0.11 · regional, not allelic
Overall
CADD	6.138	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CES4A
Protein: p.Cys515Arg
Coding: c.1543T>C
MANE Select: NM_001364782
Type: single nucleotide variant
Location: chr16:67008999 (GRCh38)
Gene constraint: LOEUF 0.953 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.64

Full CES4A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CES4A p.Ala127Thr Uncertain significance ★ ⚠ same type
CES4A p.Ala158Val Uncertain significance ★ ⚠ same type
CES4A p.Ala185Glu Uncertain significance ★ ⚠ same type
CES4A p.Ala222Glu Uncertain significance ★ ⚠ same type
CES4A p.Ala224Thr Uncertain significance ★ ⚠ same type
CES4A p.Ala236Val Uncertain significance ★ ⚠ same type
CES4A p.Ala250Val Uncertain significance ★ ⚠ same type
CES4A p.Ala271Thr 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/ces4a-p-cys515arg (accessed [today's date]).

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