Is ELANE p.Ala86Val (c.257C>T) pathogenic?

ELANE p.Ala86Val (c.257C>T) is classified Uncertain significance in ELANE (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-21). AlphaMissense: likely benign (0.2946); Very rare (popmax 0.00246%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ELANE p.Ala86Val (c.257C>T)?

ELANE p.Ala86Val (c.257C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ELANE p.Ala86Val (c.257C>T) in the general population?

ELANE p.Ala86Val (c.257C>T) is very rare (popmax 0.00246%, nfe) (gnomAD).

What do computational predictors say about ELANE p.Ala86Val (c.257C>T)?

AlphaMissense predicts likely benign (score 0.2946) — an in-silico prediction, not a clinical call.

ELANE p.Ala86Val

c.257C>T · VCV3507775

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2946 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00246%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2946	likely benign
REVEL	0.441	indeterminate
SaProt	LLR -9.55	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP 1.1, phastCons 0.89
Regional constraint	o/e 1.04	unconstrained · MANE · 3,171 bp · p 0.52 · regional, not allelic
Overall
CADD	18.37	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00246% European (non-Finnish) · 29/1,178,652 alleles

Filtering AF 0.00173% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00149%

Overall 0.00186% 30/1,609,904 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00246%	40,643
South Asian	0.0011%	90,684

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.Ala86Val
Coding: c.257C>T
MANE Select: NM_001972
Type: single nucleotide variant
Location: chr19:853294 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB
Residue 86: the peptidase s1 domain

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.Ala86Ser Uncertain significance ★★ ⚠ same residue
ELANE p.Ala86= Likely benign ★ 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-ala86val (accessed [today's date]).

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