Is ESCO2 p.Phe384Ser (c.1151T>C) pathogenic?

ESCO2 p.Phe384Ser (c.1151T>C) is classified Uncertain significance in ESCO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-04). AlphaMissense: likely pathogenic (0.8687); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ESCO2 p.Phe384Ser (c.1151T>C)?

ESCO2 p.Phe384Ser (c.1151T>C) is associated with Inborn genetic diseases (ClinVar).

How common is ESCO2 p.Phe384Ser (c.1151T>C) in the general population?

ESCO2 p.Phe384Ser (c.1151T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ESCO2 p.Phe384Ser (c.1151T>C)?

AlphaMissense predicts likely pathogenic (score 0.8687) — an in-silico prediction, not a clinical call.

ESCO2 p.Phe384Ser

c.1151T>C · rs1319521332 · VCV2269470

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8687 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8687	likely pathogenic
REVEL	0.841	moderately pathogenic-leaning
SaProt	LLR -12.14	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.9, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 28 kb · p 0.82 · regional, not allelic
Overall
CADD	27.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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: ESCO2
Protein: p.Phe384Ser
Coding: c.1151T>C
MANE Select: NM_001017420
dbSNP: rs1319521332
Type: single nucleotide variant
Location: chr8:27788866 (GRCh38)
Gene constraint: LOEUF 1.013 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 58.81

Full ESCO2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ESCO2 p.Phe384= Likely benign ★ same residue
ESCO2 p.Arg427Cys Uncertain significance ★★ ⚠ same condition
ESCO2 p.Asp17Gly Uncertain significance ★★ ⚠ same condition
ESCO2 p.Gln344Pro Uncertain significance ★★ ⚠ same condition
ESCO2 p.His412Tyr Uncertain significance ★★ ⚠ same condition
ESCO2 p.Ile449Val Uncertain significance ★★ ⚠ same condition
ESCO2 p.Leu583Ser Uncertain significance ★★ ⚠ same condition
ESCO2 p.Lys221Ile Uncertain significance ★★ ⚠ same condition

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/esco2-p-phe384ser (accessed [today's date]).

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