Is ESCO2 p.Arg293fs (c.879_880del) pathogenic?

ESCO2 p.Arg293fs (c.879880del) is classified Pathogenic in ESCO2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-21). Very rare (popmax 0.00656%, nfe); Associated with Roberts-SC phocomelia syndrome.

What condition is associated with ESCO2 p.Arg293fs (c.879_880del)?

ESCO2 p.Arg293fs (c.879_880del) is associated with Roberts-SC phocomelia syndrome, Juberg-Hayward syndrome (ClinVar).

How common is ESCO2 p.Arg293fs (c.879_880del) in the general population?

ESCO2 p.Arg293fs (c.879_880del) is very rare (popmax 0.00656%, nfe) (gnomAD).

ESCO2 p.Arg293fs

c.879_880del · rs80359857 · VCV21251

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00656%, nfe)

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 4 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.93	GERP -2.6, phastCons 0.006
Overall
CADD	22.9	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00656% European (non-Finnish) · 77/1,174,246 alleles

Filtering AF 0.00532% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00492%

Overall 0.0056% 90/1,606,126 alleles · very rare exomes 87/1,454,408 · genomes 3/151,718 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00656%	15,250
Remaining individualsnot grpmax-eligible	0.00643%	15,558
East Asian	0.00447%	22,372
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,504
South Asian	0.00332%	30,089
African / African-American	0.00268%	37,277
Finnishnot grpmax-eligible	0.00157%	63,856

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ESCO2
Protein: p.Arg293fs
Coding: c.879_880del
MANE Select: NM_001017420
dbSNP: rs80359857
Type: Microsatellite
Location: chr8:27780189 (GRCh38)
Gene constraint: LOEUF 1.013 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 58.81
Residue 293: the 'disordered' region

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 p.Arg293Gly Uncertain significance ⚠ same residue
ESCO2 p.Arg99fs Pathogenic ★★ same condition
ESCO2 p.Asn66fs Pathogenic/Likely pathogenic ★★ same condition
ESCO2 p.Glu104_Ser105insTer Pathogenic/Likely pathogenic ★★ same condition
ESCO2 p.Leu480fs Pathogenic/Likely pathogenic ★★ same condition
ESCO2 p.Lys135del Uncertain significance ★ same condition
ESCO2 c.955+7_955+8del Likely benign ★ same condition
ESCO2 c.1013+1G>A Likely 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-arg293fs (accessed [today's date]).

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