Is ELANE p.Cys71Phe (c.212G>T) pathogenic?

ELANE p.Cys71Phe (c.212G>T) is classified Pathogenic/Likely pathogenic in ELANE (ClinVar, Multiple submitters, 3 submitters; last evaluated 2015-03-07). AlphaMissense: likely pathogenic (0.9805); Absent from gnomAD v4.1; Associated with neutropenia, severe congenital, 1, autosomal dominant.

What condition is associated with ELANE p.Cys71Phe (c.212G>T)?

ELANE p.Cys71Phe (c.212G>T) is associated with neutropenia, severe congenital, 1, autosomal dominant (ClinVar).

How common is ELANE p.Cys71Phe (c.212G>T) in the general population?

ELANE p.Cys71Phe (c.212G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ELANE p.Cys71Phe (c.212G>T)?

AlphaMissense predicts likely pathogenic (score 0.9805) — an in-silico prediction, not a clinical call.

ELANE p.Cys71Phe

Q: How is Autosomal dominant severe congenital neutropenia inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.212G>T · rs878855315 · VCV242278

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9805 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,565,126)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neutropenia, severe congenital, 1, autosomal dominant

Computational evidence

Protein change
AlphaMissense	0.9805	likely pathogenic ✓ concordant with ClinVar · top 5% in ELANE
REVEL	0.82	moderately pathogenic-leaning
SaProt	LLR -14.95	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 1.1, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 3,171 bp · p 0.52 · regional, not allelic
Overall
CADD	25.0	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

No allele count reported in gnomAD v4.1 (AN 1,565,126). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ELANE
Protein: p.Cys71Phe
Coding: c.212G>T
MANE Select: NM_001972
dbSNP: rs878855315
Type: single nucleotide variant
Location: chr19:853020 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB
Residue 71: a disulfide bond; an α-helix; the peptidase s1 domain; a UniProt-annotated variant site (in scn1)

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

Disease context

neutropenia, severe congenital, 1, autosomal dominant — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal dominant severe congenital neutropenia (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy, Neonatal
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

ELANE p.Cys71Ter Uncertain significance ★★ same residue
ELANE p.Cys71= Likely benign ★★ same residue
ELANE p.Cys71Arg Pathogenic same residue
ELANE p.Cys71Trp 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

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-cys71phe (accessed [today's date]).

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