Is ELANE p.Ala195Pro (c.583G>C) pathogenic?

ELANE p.Ala195Pro (c.583G>C) is classified Uncertain significance in ELANE (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-31). AlphaMissense: likely pathogenic (0.7141); Very rare (popmax 0.0022%, sas); Associated with Inborn genetic diseases.

What condition is associated with ELANE p.Ala195Pro (c.583G>C)?

ELANE p.Ala195Pro (c.583G>C) is associated with Inborn genetic diseases (ClinVar).

How common is ELANE p.Ala195Pro (c.583G>C) in the general population?

ELANE p.Ala195Pro (c.583G>C) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about ELANE p.Ala195Pro (c.583G>C)?

AlphaMissense predicts likely pathogenic (score 0.7141) — an in-silico prediction, not a clinical call.

ELANE p.Ala195Pro

c.583G>C · VCV4017410

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7141 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7141	likely pathogenic
REVEL	0.554	indeterminate
SaProt	LLR -11.09	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.2	GERP 2.1, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 3,171 bp · p 0.52 · regional, not allelic
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0022% South Asian · 2/91,018 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000249% 4/1,608,710 alleles · very rare exomes 4/1,456,340 · genomes 0/152,370 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,509
Remaining individualsnot grpmax-eligible	0.0016%	62,330
European (non-Finnish)	8.47e-05%	1,179,948

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.Ala195Pro
Coding: c.583G>C
MANE Select: NM_001972
Type: single nucleotide variant
Location: chr19:855780 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB
Residue 195: the peptidase s1 domain; a UniProt-annotated variant site (in scn1 and ch)

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.Ala195Gly Uncertain significance ★ ⚠ same residue
ELANE p.Ala195Asp Uncertain significance ★★ ⚠ same residue
ELANE p.Ala195= Likely benign ★★ same residue
ELANE p.Ala195Thr Uncertain significance ★ ⚠ 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

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-ala195pro (accessed [today's date]).

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