Is ELP1 p.Pro1111fs (c.3332del) pathogenic?

ELP1 p.Pro1111fs (c.3332del) is classified Likely pathogenic in ELP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-30). Very rare (popmax 0.00167%, amr); Associated with Riley-Day syndrome.

What condition is associated with ELP1 p.Pro1111fs (c.3332del)?

ELP1 p.Pro1111fs (c.3332del) is associated with Riley-Day syndrome (ClinVar).

How common is ELP1 p.Pro1111fs (c.3332del) in the general population?

ELP1 p.Pro1111fs (c.3332del) is very rare (popmax 0.00167%, amr) (gnomAD).

How is Familial dysautonomia inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ELP1 p.Pro1111fs

c.3332del · VCV4815224

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

Riley-Day 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 31 of 37
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.6	GERP 0.46, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,974 alleles

Overall 7.01e-05% 1/1,426,834 alleles · very rare

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: ELP1
Protein: p.Pro1111fs
Coding: c.3332del
MANE Select: NM_003640
Type: Deletion
Location: chr9:108881719 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.31 · 5 PDB
Residue 1111: the 'mediates dimerization' region; an α-helix

Full ELP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Riley-Day syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial dysautonomia (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

ELP1 p.Pro1111Ala Uncertain significance ★ ⚠ same residue
ELP1 c.2860+1_2860+7del Likely pathogenic ★★ same condition
ELP1 c.2958+1del Likely pathogenic ★★ same condition
ELP1 c.954_958+7del Likely pathogenic ★★ same condition
ELP1 p.Asn225fs Pathogenic/Likely pathogenic ★★ same condition
ELP1 p.Asn384_Ser385insTer Pathogenic/Likely pathogenic ★★ same condition
ELP1 p.Asp495fs Pathogenic/Likely pathogenic ★★ same condition
ELP1 p.Cys319fs Pathogenic/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/elp1-p-pro1111fs (accessed [today's date]).

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