Is ELANE p.Val65Asp (c.194T>A) pathogenic?

ELANE p.Val65Asp (c.194T>A) is classified Likely pathogenic in ELANE (ClinVar, Single submitter, 1 submitter; last evaluated 2016-01-05). AlphaMissense: likely pathogenic (0.9947); Absent from gnomAD v4.1.

How common is ELANE p.Val65Asp (c.194T>A) in the general population?

ELANE p.Val65Asp (c.194T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ELANE p.Val65Asp (c.194T>A)?

AlphaMissense predicts likely pathogenic (score 0.9947) — an in-silico prediction, not a clinical call.

ELANE p.Val65Asp

c.194T>A · rs2035617899 · VCV988480

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9947 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9947	likely pathogenic ✓ concordant with ClinVar · top 1% in ELANE
REVEL	0.853	moderately pathogenic-leaning
SaProt	LLR -14.68	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 0.52, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 3,171 bp · p 0.52 · regional, not allelic
Overall
CADD	24.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ELANE
Protein: p.Val65Asp
Coding: c.194T>A
MANE Select: NM_001972
dbSNP: rs2035617899
Type: single nucleotide variant
Location: chr19:853002 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB
Residue 65: a disulfide bond; a β-strand; 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

Similar variants

ELANE p.Val65Leu Uncertain significance ★ ⚠ same residue
ELANE p.Val65Phe Uncertain significance ★ ⚠ same residue
ELANE c.597+1G>A Pathogenic ★★ same type
ELANE c.597+1G>C Pathogenic ★★ same type
ELANE c.597+1G>T Pathogenic ★★ same type
ELANE c.597+5G>A Pathogenic/Likely pathogenic ★★ same type
ELANE p.Ala57Thr Pathogenic/Likely pathogenic ★★ same type
ELANE p.Ala57Val Pathogenic/Likely 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-p-val65asp (accessed [today's date]).

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