Is ELANE p.Ala68= (c.204C>T) pathogenic?

ELANE p.Ala68= (c.204C>T) is classified Benign/Likely benign in ELANE (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-24). Very rare (popmax 0.00234%, eas); Associated with Inborn genetic diseases.

What condition is associated with ELANE p.Ala68= (c.204C>T)?

ELANE p.Ala68= (c.204C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ELANE p.Ala68= (c.204C>T) in the general population?

ELANE p.Ala68= (c.204C>T) is very rare (popmax 0.00234%, eas) (gnomAD).

ELANE p.Ala68=

c.204C>T · rs1568304177 · VCV1233974

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00234%, eas)

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 -9.8	GERP -4.7
Overall
CADD	1.644	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00234% East Asian · 1/42,822 alleles

Overall 0.000127% 2/1,569,310 alleles · very rare exomes 2/1,417,014 · genomes 0/152,296 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00234%	42,822
South Asian	0.00115%	87,132

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.Ala68=
Coding: c.204C>T
MANE Select: NM_001972
dbSNP: rs1568304177
Type: single nucleotide variant
Location: chr19:853012 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB
Residue 68: 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.Ala68Asp Uncertain significance ★★ ⚠ same residue
ELANE p.Ala40Val 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
ELANE p.Arg91Gln 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-ala68 (accessed [today's date]).

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