Is ELANE p.Val31fs (c.91del) pathogenic?

ELANE p.Val31fs (c.91del) is classified Likely pathogenic in ELANE (ClinVar, Single submitter, 1 submitter; last evaluated 2017-10-02). Very rare (popmax 6.92e-05%); Associated with autoinflammatory syndrome.

What condition is associated with ELANE p.Val31fs (c.91del)?

ELANE p.Val31fs (c.91del) is associated with autoinflammatory syndrome (ClinVar).

How common is ELANE p.Val31fs (c.91del) in the general population?

ELANE p.Val31fs (c.91del) is very rare (popmax 6.92e-05%) (gnomAD).

ELANE p.Val31fs

c.91del · rs2145143911 · VCV1694275

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 6.92e-05%)

Conditions

autoinflammatory 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 2 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -5.6	GERP -4.4

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.92e-05%

Overall 6.92e-05% 1/1,444,364 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: ELANE
Protein: p.Val31fs
Coding: c.91del
MANE Select: NM_001972
dbSNP: rs2145143911
Type: Deletion
Location: chr19:852899 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB
Residue 31: the peptidase s1 domain

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

Disease context

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

Similar variants

ELANE p.Val31= Conflicting classifications of pathogenicity ★ same residue
ELANE p.Val31Leu Uncertain significance ★ ⚠ same residue
ELANE p.Val31Met Uncertain significance ★ ⚠ same residue
ELANE p.Ala61Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
ELANE p.Arg92Gln Uncertain significance ★★ ⚠ same condition
ELANE p.Gly148Arg Uncertain significance ★★ ⚠ same condition
ELANE p.Gly226Arg Uncertain significance ★★ ⚠ same condition
ELANE p.Gly23Asp 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/elane-p-val31fs (accessed [today's date]).

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