Is ELANE p.Ile30Met (c.90T>G) pathogenic?

ELANE p.Ile30Met (c.90T>G) is classified Likely pathogenic in ELANE (ClinVar, Single submitter, 1 submitter; last evaluated 2016-01-05). AlphaMissense: ambiguous (0.5518); Absent from gnomAD v4.1.

How common is ELANE p.Ile30Met (c.90T>G) in the general population?

ELANE p.Ile30Met (c.90T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ELANE p.Ile30Met (c.90T>G)?

AlphaMissense predicts ambiguous (score 0.5518) — an in-silico prediction, not a clinical call.

ELANE p.Ile30Met

c.90T>G · rs2035615592 · VCV988479

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5518 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.5518	ambiguous
REVEL	0.618	indeterminate
SaProt	LLR -11.54	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.6	GERP -4.4
Regional constraint	o/e 1.02	unconstrained · MANE · 597 bp · p 0.86 · regional, not allelic
Overall
CADD	18.77	PHRED · no single calibrated threshold — expert panels disagree

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: ELANE
Protein: p.Ile30Met
Coding: c.90T>G
MANE Select: NM_001972
dbSNP: rs2035615592
Type: single nucleotide variant
Location: chr19:852898 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB
Residue 30: the peptidase s1 domain

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

Similar variants

ELANE c.597+1G>A Pathogenic ★★ same type
ELANE c.597+1G>C Pathogenic ★★ same type
ELANE c.597+1G>T Pathogenic ★★ same type
ELANE c.597+5G>A Pathogenic/Likely pathogenic ★★ same type
ELANE p.Ala57Thr Pathogenic/Likely pathogenic ★★ same type
ELANE p.Ala57Val Pathogenic/Likely pathogenic ★★ same type
ELANE p.Ala61Val Pathogenic/Likely pathogenic ★★ ⚠ same type
ELANE p.Arg103Leu Likely pathogenic ★★ ⚠ same type

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-ile30met (accessed [today's date]).

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