Is ELANE p.Ala61Val (c.182C>T) pathogenic?

ELANE p.Ala61Val (c.182C>T) is classified Pathogenic/Likely pathogenic in ELANE (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-09-02). AlphaMissense: ambiguous (0.4296); Very rare (popmax 8.55e-05%, nfe); Associated with ELANE-related disorders.

What condition is associated with ELANE p.Ala61Val (c.182C>T)?

ELANE p.Ala61Val (c.182C>T) is associated with ELANE-related disorders, cyclic neutropenia, autoinflammatory syndrome (ClinVar).

How common is ELANE p.Ala61Val (c.182C>T) in the general population?

ELANE p.Ala61Val (c.182C>T) is very rare (popmax 8.55e-05%, nfe) (gnomAD).

What do computational predictors say about ELANE p.Ala61Val (c.182C>T)?

AlphaMissense predicts ambiguous (score 0.4296) — an in-silico prediction, not a clinical call.

ELANE p.Ala61Val

c.182C>T · rs137854447 · VCV16740

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

ambiguous

0.4296 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.55e-05%, nfe)

Conditions

ELANE-related disorders

Computational evidence

Protein change
AlphaMissense	0.4296	ambiguous
REVEL	0.575	indeterminate
SaProt	LLR -11.97	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -0.046, phastCons 0.003
Regional constraint	o/e 1.04	unconstrained · MANE · 3,171 bp · p 0.52 · regional, not allelic
Overall
CADD	16.87	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 8.55e-05% European (non-Finnish) · 1/1,169,904 alleles

Overall 6.33e-05% 1/1,579,780 alleles · very rare exomes 1/1,427,446 · genomes 0/152,334 · joint denominator

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.Ala61Val
Coding: c.182C>T
MANE Select: NM_001972
dbSNP: rs137854447
Type: single nucleotide variant
Location: chr19:852990 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB
Residue 61: a β-strand; the peptidase s1 domain; a UniProt-annotated variant site (sequence variant); a UniProt-annotated variant site (in scn1 and ch)

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

Disease context

ELANE-related disorders

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

Similar variants

ELANE p.Ala61Glu Uncertain significance ★ ⚠ same residue
ELANE p.Ala61= Likely benign ★ 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
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-ala61val (accessed [today's date]).

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