Is ELANE p.Gly4Arg (c.10G>C) pathogenic?

ELANE p.Gly4Arg (c.10G>C) is classified Uncertain significance in ELANE (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-24). AlphaMissense: likely benign (0.1383); Very rare (popmax 0.0011%, sas); Associated with ELANE-related disorder.

What condition is associated with ELANE p.Gly4Arg (c.10G>C)?

ELANE p.Gly4Arg (c.10G>C) is associated with ELANE-related disorder (ClinVar).

How common is ELANE p.Gly4Arg (c.10G>C) in the general population?

ELANE p.Gly4Arg (c.10G>C) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about ELANE p.Gly4Arg (c.10G>C)?

AlphaMissense predicts likely benign (score 0.1383) — an in-silico prediction, not a clinical call.

ELANE p.Gly4Arg

c.10G>C · rs773460580 · VCV2635364

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1383 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

ELANE-related disorder

Computational evidence

Protein change
AlphaMissense	0.1383	likely benign
REVEL	0.354	indeterminate
SaProt	LLR -6.43	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 -0.2	GERP -3.3
Regional constraint	o/e 1.02	unconstrained · MANE · 597 bp · p 0.86 · regional, not allelic
Overall
CADD	0.104	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 0.0011% South Asian · 1/90,996 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000412% 6/1,457,640 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	90,996
European (non-Finnish)	0.000424%	235,965

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.Gly4Arg
Coding: c.10G>C
MANE Select: NM_001972
dbSNP: rs773460580
Type: single nucleotide variant
Location: chr19:852338 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB

Full ELANE gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ELANE-related disorder

Similar variants

ELANE p.Gly4Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
ELANE p.Gly4= Likely benign ★ same residue
ELANE c.597+1G>T Pathogenic ★★ same condition
ELANE p.Ala61Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
ELANE p.Arg103Leu Likely pathogenic ★★ ⚠ same condition
ELANE p.Arg220Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
ELANE p.Gly214Arg Pathogenic ★★ same condition
ELANE p.Leu84Pro Pathogenic/Likely pathogenic ★★ 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-gly4arg (accessed [today's date]).

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