Is ELANE p.His53Pro (c.158A>C) pathogenic?

ELANE p.His53Pro (c.158A>C) is classified Uncertain significance in ELANE (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-01). AlphaMissense: likely pathogenic (0.7483); Absent from gnomAD v4.1.

How common is ELANE p.His53Pro (c.158A>C) in the general population?

ELANE p.His53Pro (c.158A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ELANE p.His53Pro (c.158A>C)?

AlphaMissense predicts likely pathogenic (score 0.7483) — an in-silico prediction, not a clinical call.

ELANE p.His53Pro

c.158A>C · rs2512164539 · VCV2571021

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7483 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7483	likely pathogenic
REVEL	0.844	moderately pathogenic-leaning
SaProt	LLR -12.04	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 8.7	GERP 0.57, phastCons 1
Regional constraint	o/e 0.31	constrained · MANE · 62 bp · p 0.00023 · regional, not allelic
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.His53Pro
Coding: c.158A>C
MANE Select: NM_001972
dbSNP: rs2512164539
Type: single nucleotide variant
Location: chr19:852966 (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

Similar variants

ELANE p.His53Arg Likely pathogenic ★ same residue
ELANE p.His53Asp 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 c.597+1G>A Pathogenic ★★ same type
ELANE c.597+1G>C Pathogenic ★★ same type
ELANE c.597+1G>T 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-his53pro (accessed [today's date]).

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