Is ELANE p.Ile245Thr (c.734T>C) pathogenic?

ELANE p.Ile245Thr (c.734T>C) is classified Uncertain significance in ELANE (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). AlphaMissense: ambiguous (0.4948); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ELANE p.Ile245Thr (c.734T>C)?

ELANE p.Ile245Thr (c.734T>C) is associated with Inborn genetic diseases (ClinVar).

How common is ELANE p.Ile245Thr (c.734T>C) in the general population?

ELANE p.Ile245Thr (c.734T>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about ELANE p.Ile245Thr (c.734T>C)?

AlphaMissense predicts ambiguous (score 0.4948) — an in-silico prediction, not a clinical call.

ELANE p.Ile245Thr

c.734T>C · VCV4618390

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4948 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4948	ambiguous
REVEL	0.503	indeterminate
SaProt	LLR -9.88	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 2, phastCons 0.7
Regional constraint	o/e 1.04	unconstrained · MANE · 3,171 bp · p 0.52 · regional, not allelic
Overall
CADD	20.4	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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,010 alleles

Overall 6.84e-05% 1/1,461,006 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.Ile245Thr
Coding: c.734T>C
MANE Select: NM_001972
Type: single nucleotide variant
Location: chr19:856094 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB
Residue 245: an α-helix; the peptidase s1 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ELANE p.Ile245Val Likely benign ★ same residue
ELANE p.Ile245= Likely benign ★ same residue
ELANE p.Ala40Val Uncertain significance ★★ ⚠ same condition
ELANE p.Ala68Asp Uncertain significance ★★ ⚠ same condition
ELANE p.Ala79Thr Uncertain significance ★★ ⚠ same condition
ELANE p.Arg183Cys Uncertain significance ★★ ⚠ same condition
ELANE p.Arg248His Uncertain significance ★★ ⚠ same condition
ELANE p.Arg78Leu 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-ile245thr (accessed [today's date]).

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