Is ELANE p.His53Asp (c.157C>G) pathogenic?

ELANE p.His53Asp (c.157C>G) is classified Likely pathogenic in ELANE (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). AlphaMissense: likely pathogenic (0.9308); Absent from gnomAD v4.1; Associated with ELANE-related disorder.

What condition is associated with ELANE p.His53Asp (c.157C>G)?

ELANE p.His53Asp (c.157C>G) is associated with ELANE-related disorder (ClinVar).

How common is ELANE p.His53Asp (c.157C>G) in the general population?

ELANE p.His53Asp (c.157C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ELANE p.His53Asp (c.157C>G)?

AlphaMissense predicts likely pathogenic (score 0.9308) — an in-silico prediction, not a clinical call.

ELANE p.His53Asp

c.157C>G · rs1131691882 · VCV2630360

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9308 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ELANE-related disorder

Computational evidence

Protein change
AlphaMissense	0.9308	likely pathogenic ✓ concordant with ClinVar
REVEL	0.705	pathogenic-leaning
SaProt	LLR -14.40	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 5.5	GERP 1.2, phastCons 1
Regional constraint	o/e 0.31	constrained · MANE · 62 bp · p 0.00023 · regional, not allelic
Overall
CADD	24.6	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

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.His53Asp
Coding: c.157C>G
MANE Select: NM_001972
dbSNP: rs1131691882
Type: single nucleotide variant
Location: chr19:852965 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB
Residue 53: a β-strand; a UniProt-annotated variant site (in scn1); a UniProt-annotated variant site (in ch); the peptidase s1 domain

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

Disease context

ELANE-related disorder

Similar variants

ELANE p.His53Arg Likely pathogenic ★ same residue
ELANE p.His53Gln Likely pathogenic ★ same residue
ELANE p.His53Leu Likely pathogenic ★ same residue
ELANE p.His53Tyr Likely pathogenic ★ same residue
ELANE p.His53Pro Uncertain significance ★ ⚠ same residue
ELANE c.597+1G>T Pathogenic ★★ same condition
ELANE p.Ala61Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
ELANE p.Arg103Leu 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/elane-p-his53asp (accessed [today's date]).

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