Is ESYT2 p.Ser59Arg (c.177C>A) pathogenic?

ESYT2 p.Ser59Arg (c.177C>A) is classified Uncertain significance in ESYT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). AlphaMissense: likely pathogenic (0.9934); Absent from gnomAD v4.1.

How common is ESYT2 p.Ser59Arg (c.177C>A) in the general population?

ESYT2 p.Ser59Arg (c.177C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ESYT2 p.Ser59Arg (c.177C>A)?

AlphaMissense predicts likely pathogenic (score 0.9934) — an in-silico prediction, not a clinical call.

ESYT2 p.Ser59Arg

c.177C>A · rs2535894910 · VCV2492399

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9934 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,528,744)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9934	likely pathogenic · top 5% in ESYT2
REVEL	0.944	strongly pathogenic-leaning
SaProt	LLR -8.57	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.4	GERP 2.2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 95 kb · p 0.024 · regional, not allelic
Overall
CADD	25.5	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 S135R vs ClinVar S59R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,528,744). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ESYT2
Protein: p.Ser59Arg
Coding: c.177C>A
MANE Select: NM_001367773
dbSNP: rs2535894910
Type: single nucleotide variant
Location: chr7:158829242 (GRCh38)
Gene constraint: LOEUF 0.684 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.44 · 4 PDB
Residue 59: the 'disordered' region

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-ser59arg (accessed [today's date]).

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