Is ELANE p.Trp241Cys (c.723G>T) pathogenic?

ELANE p.Trp241Cys (c.723G>T) is classified Likely pathogenic in ELANE (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-22). AlphaMissense: likely pathogenic (0.9962); Very rare (popmax 8.48e-05%, nfe).

How common is ELANE p.Trp241Cys (c.723G>T) in the general population?

ELANE p.Trp241Cys (c.723G>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about ELANE p.Trp241Cys (c.723G>T)?

AlphaMissense predicts likely pathogenic (score 0.9962) — an in-silico prediction, not a clinical call.

ELANE p.Trp241Cys

c.723G>T · VCV3338707

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9962 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9962	likely pathogenic ✓ concordant with ClinVar · top 1% in ELANE
REVEL	0.857	moderately pathogenic-leaning
SaProt	LLR -16.70	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 3,171 bp · p 0.52 · regional, not allelic
Overall
CADD	25.6	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 8.48e-05% European (non-Finnish) · 1/1,179,822 alleles

Overall 6.85e-05% 1/1,460,898 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.Trp241Cys
Coding: c.723G>T
MANE Select: NM_001972
Type: single nucleotide variant
Location: chr19:856083 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB
Residue 241: an α-helix; the peptidase s1 domain

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

Similar variants

ELANE p.Trp241Ter Pathogenic ★ same residue
ELANE p.Trp241Gly Uncertain significance ★ ⚠ same residue
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

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-trp241cys (accessed [today's date]).

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