Is ESYT2 p.Pro387Arg (c.1160C>G) pathogenic?

ESYT2 p.Pro387Arg (c.1160C>G) is classified Uncertain significance in ESYT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-28). AlphaMissense: ambiguous (0.5058); Absent from gnomAD v4.1.

How common is ESYT2 p.Pro387Arg (c.1160C>G) in the general population?

ESYT2 p.Pro387Arg (c.1160C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ESYT2 p.Pro387Arg (c.1160C>G)?

AlphaMissense predicts ambiguous (score 0.5058) — an in-silico prediction, not a clinical call.

ESYT2 p.Pro387Arg

c.1160C>G · VCV3510488

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5058 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.5058	ambiguous
REVEL	0.403	indeterminate
SaProt	LLR -7.06	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 95 kb · p 0.024 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P463R vs ClinVar P387R) — verify the residue.

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: ESYT2
Protein: p.Pro387Arg
Coding: c.1160C>G
MANE Select: NM_001367773
Type: single nucleotide variant
Location: chr7:158763107 (GRCh38)
Gene constraint: LOEUF 0.684 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.44 · 4 PDB
Residue 387: the c2 1 domain; a β-strand

Full ESYT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ESYT2 c.26C>T Uncertain significance ★ same type
ESYT2 c.43C>G Uncertain significance ★ same type
ESYT2 c.-17C>G Uncertain significance ★ same type
ESYT2 c.-38C>T Uncertain significance ★ ⚠ same type
ESYT2 c.-41A>C Uncertain significance ★ ⚠ same type
ESYT2 c.-55C>G Uncertain significance ★ same type
ESYT2 c.-59G>A Uncertain significance ★ ⚠ same type
ESYT2 c.-62C>G 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/esyt2-p-pro387arg (accessed [today's date]).

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