Is ELANE p.Ala69= (c.207G>T) pathogenic?

ELANE p.Ala69= (c.207G>T) is classified Likely benign in ELANE (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-22). Ultra-rare (popmax 0.0173%, mid); Associated with Inborn genetic diseases.

What condition is associated with ELANE p.Ala69= (c.207G>T)?

ELANE p.Ala69= (c.207G>T) is associated with Inborn genetic diseases (ClinVar).

How common is ELANE p.Ala69= (c.207G>T) in the general population?

ELANE p.Ala69= (c.207G>T) is ultra-rare (popmax 0.0173%, mid) (gnomAD).

ELANE p.Ala69=

c.207G>T · VCV3844304

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0173%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.5	GERP -4.7
Overall
CADD	1.292	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0173% Middle Eastern · 1/5,772 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00203%

Overall 0.00177% 25/1,413,952 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0173%	5,772
South Asian	0.00691%	14,474
Remaining individualsnot grpmax-eligible	0.00328%	30,502
European (non-Finnish)	0.00138%	72,703

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.Ala69=
Coding: c.207G>T
MANE Select: NM_001972
Type: single nucleotide variant
Location: chr19:853015 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB
Residue 69: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ELANE p.Ala69Thr Uncertain significance ★★ ⚠ same residue
ELANE p.Ala40Val Uncertain significance ★★ ⚠ same condition
ELANE p.Ala68Asp Uncertain significance ★★ ⚠ same condition
ELANE p.Ala79Thr Uncertain significance ★★ ⚠ same condition
ELANE p.Arg183Cys Uncertain significance ★★ ⚠ same condition
ELANE p.Arg248His Uncertain significance ★★ ⚠ same condition
ELANE p.Arg78Leu Uncertain significance ★★ ⚠ same condition
ELANE p.Arg78Ser Uncertain significance ★★ ⚠ 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-ala69 (accessed [today's date]).

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