Is ELANE p.Val101= (c.303G>A) pathogenic?

ELANE p.Val101= (c.303G>A) is classified Benign/Likely benign in ELANE (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-05). Very rare (popmax 0.00267%, afr); Associated with Inborn genetic diseases.

What condition is associated with ELANE p.Val101= (c.303G>A)?

ELANE p.Val101= (c.303G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ELANE p.Val101= (c.303G>A) in the general population?

ELANE p.Val101= (c.303G>A) is very rare (popmax 0.00267%, afr) (gnomAD).

ELANE p.Val101=

c.303G>A · rs1330923988 · VCV1266501

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

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 -0.57	GERP -4.5
Overall
CADD	2.491	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,882 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,611,370 alleles · very rare exomes 0/1,459,150 · genomes 2/152,220 · 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.Val101=
Coding: c.303G>A
MANE Select: NM_001972
dbSNP: rs1330923988
Type: single nucleotide variant
Location: chr19:853340 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB
Residue 101: a β-strand; the peptidase s1 domain; a UniProt-annotated variant site (in scn1; located on the same allele as l-98; reduces proteolytic enzyme activity by slightly less than half; together with l-98 shows an additive effect with minimal remaining enzyme activity); 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.Val101Met Pathogenic ★★ same residue
ELANE p.Val101Gly Pathogenic 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

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-val101 (accessed [today's date]).

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