Is ELANE p.Met1Val (c.1A>G) pathogenic?

ELANE p.Met1Val (c.1A>G) is classified Pathogenic in ELANE (ClinVar, Multiple submitters, 4 submitters; last evaluated 2021-12-20). Absent from gnomAD v4.1; Associated with ELANE-related disorders.

What condition is associated with ELANE p.Met1Val (c.1A>G)?

ELANE p.Met1Val (c.1A>G) is associated with ELANE-related disorders, cyclic neutropenia, neutropenia, severe congenital, 1, autosomal dominant (ClinVar).

How common is ELANE p.Met1Val (c.1A>G) in the general population?

ELANE p.Met1Val (c.1A>G) is absent from gnomAD v4.1 (gnomAD).

ELANE p.Met1Val

c.1A>G · rs2145142832 · VCV1343367

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

start-loss

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

ELANE-related disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function
REVEL	0.608	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP 0.77, phastCons 1
Overall
CADD	16.86	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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.Met1Val
Coding: c.1A>G
MANE Select: NM_001972
dbSNP: rs2145142832
Type: single nucleotide variant
Location: chr19:852329 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB

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

Disease context

ELANE-related disorders

Also linked: cyclic neutropenia neutropenia, severe congenital, 1, autosomal dominant

Similar variants

ELANE p.Met1Ile Pathogenic/Likely pathogenic ★★ same residue
ELANE p.Met1Leu Likely pathogenic same residue
ELANE p.Met1Thr Pathogenic/Likely pathogenic ★★ same residue
ELANE c.597+1G>A Pathogenic ★★ same condition
ELANE c.597+1G>C Pathogenic ★★ same condition
ELANE c.597+1G>T Pathogenic ★★ same condition
ELANE c.597+5G>A Pathogenic/Likely pathogenic ★★ same condition
ELANE p.Ala57Thr Pathogenic/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-met1val (accessed [today's date]).

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