Is ELANE p.Ala57Val (c.170C>T) pathogenic?

ELANE p.Ala57Val (c.170C>T) is classified Pathogenic/Likely pathogenic in ELANE (ClinVar, Multiple submitters, 2 submitters; last evaluated 2020-10-23). AlphaMissense: likely pathogenic (0.9212); Absent from gnomAD v4.1.

How common is ELANE p.Ala57Val (c.170C>T) in the general population?

ELANE p.Ala57Val (c.170C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ELANE p.Ala57Val (c.170C>T)?

AlphaMissense predicts likely pathogenic (score 0.9212) — an in-silico prediction, not a clinical call.

ELANE p.Ala57Val

c.170C>T · rs1057520110 · VCV377028

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9212 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9212	likely pathogenic ✓ concordant with ClinVar
REVEL	0.61	indeterminate
SaProt	LLR -14.11	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.064	GERP -4.7
Regional constraint	o/e 0.31	constrained · MANE · 62 bp · p 0.00023 · regional, not allelic
Overall
CADD	14.11	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.Ala57Val
Coding: c.170C>T
MANE Select: NM_001972
dbSNP: rs1057520110
Type: single nucleotide variant
Location: chr19:852978 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB
Residue 57: 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.Ala57Thr Pathogenic/Likely pathogenic ★★ same residue
ELANE p.Ala57= Benign/Likely benign ★★ same residue
ELANE p.Ala57Asp Pathogenic 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.Ala61Val 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-ala57val (accessed [today's date]).

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