Is ELANE p.Pro262Leu (c.785C>T) pathogenic?

ELANE p.Pro262Leu (c.785C>T) is classified Benign/Likely benign in ELANE (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-01-31). AlphaMissense: likely benign (0.0859); Low-frequency (popmax 1.53%, afr); Associated with neutropenia, severe congenital, 1, autosomal dominant.

What condition is associated with ELANE p.Pro262Leu (c.785C>T)?

ELANE p.Pro262Leu (c.785C>T) is associated with neutropenia, severe congenital, 1, autosomal dominant, cyclic neutropenia, autoinflammatory syndrome (ClinVar).

How common is ELANE p.Pro262Leu (c.785C>T) in the general population?

ELANE p.Pro262Leu (c.785C>T) is low-frequency (popmax 1.53%, afr) (gnomAD).

What do computational predictors say about ELANE p.Pro262Leu (c.785C>T)?

AlphaMissense predicts likely benign (score 0.0859) — an in-silico prediction, not a clinical call.

ELANE p.Pro262Leu

Q: How is Autosomal dominant severe congenital neutropenia inherited?

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

c.785C>T · rs17216670 · VCV137202

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

AlphaMissense

likely benign

0.0859 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.53%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neutropenia, severe congenital, 1, autosomal dominant

Computational evidence

Protein change
AlphaMissense	0.0859	likely benign
REVEL	0.266	benign-leaning
SaProt	LLR -7.53	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.46	GERP -3
Regional constraint	o/e 1.04	unconstrained · MANE · 3,171 bp · p 0.52 · regional, not allelic
Overall
CADD	12.6	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

Grpmax group 1.53% African / African-American · 1,149/75,050 alleles

Filtering AF 1.46% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.43%

Overall 0.0784% 1,264/1,612,916 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.53%	65
Remaining individualsnot grpmax-eligible	0.0784%	1,275
Admixed American	0.0683%	1,464
Middle Eastern	0.033%	3,031
South Asian	0.00439%	22,772
East Asian	0.00223%	44,884
European (non-Finnish)	0.00153%	65,557

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.Pro262Leu
Coding: c.785C>T
MANE Select: NM_001972
dbSNP: rs17216670
Type: single nucleotide variant
Location: chr19:856145 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB
Residue 262: a UniProt-annotated variant site (found in patients with severe congenital or cyclic neutropenia)

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

Also linked: cyclic neutropenia autoinflammatory syndrome

For Autosomal dominant severe congenital neutropenia (Orphanet):

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

Similar variants

ELANE p.Pro262Ser Likely benign ★★ same residue
ELANE p.Pro262= 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.Ala61Val 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-pro262leu (accessed [today's date]).

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