Is ELANE c.67+210del pathogenic?

ELANE c.67+210del is classified Benign in ELANE (ClinVar, Single submitter, 1 submitter; last evaluated 2019-08-18). Common (popmax 30.6%, sas) — too common for a highly-penetrant pathogenic allele.

ELANE c.67+210del

Q: How common is ELANE c.67+210del in the general population?

ELANE c.67+210del is common (popmax 30.6%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs371057361 · VCV1298047

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 30.6%, sas) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +210	deep intronic (+210 nt into the intron)
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -3.4	GERP -1.2
Non-coding constraint	Z 3.68	1 kb window · o/e 0.78 · regional · uncalibrated
Overall
CADD	0.635	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 30.6% South Asian · 583/1,908 alleles

Filtering AF 28.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 27.8%

Overall 27.3% 20,939/76,648 alleles · common

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	34.6%	3
South Asiangrpmax	30.6%	3
Ashkenazi Jewishnot grpmax-eligible	29.5%	3
European (non-Finnish)	28.4%	4
African / African-American	26.4%	4
Remaining individualsnot grpmax-eligible	24.5%	4
Admixed American	24.4%	4
Middle Eastern	23.3%	4
Amishnot grpmax-eligible	15.8%	6
East Asian	4.56%	22

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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
Coding: c.67+210del
MANE Select: NM_001972
dbSNP: rs371057361
Type: Deletion
Location: chr19:852595 (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

Similar variants

ELANE p.Pro111_Val112insTer Uncertain significance ★★ same type
ELANE c.597+5del Pathogenic ★ same type
ELANE p.Ala195fs Likely pathogenic ★ same type
ELANE p.Ala236fs Likely pathogenic ★ same type
ELANE p.Arg182fs Pathogenic ★ same type
ELANE p.Asn113_Ile120del Pathogenic ★ same type
ELANE p.Asp201fs Likely pathogenic ★ same type
ELANE p.Asp230fs 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-c-67-plus-210del (accessed [today's date]).

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