Is ESCO2 p.Phe479fs (c.1436_1437del) pathogenic?

ESCO2 p.Phe479fs (c.14361437del) is classified Likely pathogenic in ESCO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-13). Associated with Roberts-SC phocomelia syndrome.

What condition is associated with ESCO2 p.Phe479fs (c.1436_1437del)?

ESCO2 p.Phe479fs (c.1436_1437del) is associated with Roberts-SC phocomelia syndrome, Juberg-Hayward syndrome (ClinVar).

ESCO2 p.Phe479fs

c.1436_1437del · VCV3595519

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Roberts-SC phocomelia syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: ESCO2
Protein: p.Phe479fs
Coding: c.1436_1437del
MANE Select: NM_001017420
Type: Deletion
Location: chr8:27792748 (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

Roberts-SC phocomelia syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Juberg-Hayward syndrome

Similar variants

ESCO2 c.955+2_955+5del Pathogenic/Likely pathogenic ★★ same condition
ESCO2 p.Asn39_Ser40insTer Pathogenic/Likely pathogenic ★★ same condition
ESCO2 p.Asp292fs Pathogenic ★★ same condition
ESCO2 p.Glu239fs Likely pathogenic ★★ same condition
ESCO2 p.Ile476fs Likely pathogenic ★★ same condition
ESCO2 p.Leu26fs Pathogenic/Likely pathogenic ★★ same condition
ESCO2 p.Lys103fs Pathogenic ★★ same condition
ESCO2 p.Lys139fs Pathogenic ★★ 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-phe479fs (accessed [today's date]).

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