Is ELN p.Gly413Arg (c.1237G>C) pathogenic?

ELN p.Gly413Arg (c.1237G>C) is classified Uncertain significance in ELN (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-01). AlphaMissense: likely pathogenic (0.8233); Very rare (popmax 0.00167%, amr).

How common is ELN p.Gly413Arg (c.1237G>C) in the general population?

ELN p.Gly413Arg (c.1237G>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about ELN p.Gly413Arg (c.1237G>C)?

AlphaMissense predicts likely pathogenic (score 0.8233) — an in-silico prediction, not a clinical call.

ELN p.Gly413Arg

c.1237G>C · VCV4874656

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8233 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8233	likely pathogenic
REVEL	0.092	moderately benign-leaning
SaProt	LLR -12.54	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1	GERP 3.6, phastCons 0.004
Regional constraint	o/e 0.91	unconstrained · MANE · 41 kb · p 0.005 · regional, not allelic
Overall
CADD	21.3	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

Grpmax group 0.00167% Admixed American · 1/59,956 alleles

Overall 6.84e-05% 1/1,461,368 alleles · very rare

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: ELN
Protein: p.Gly413Arg
Coding: c.1237G>C
MANE Select: NM_000501
Type: single nucleotide variant
Location: chr7:74056357 (GRCh38)
Gene constraint: LOEUF 0.696 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 36.20

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

Similar variants

ELN p.Gly413Ala Uncertain significance ★ ⚠ same residue
ELN p.Gly413Ser Uncertain significance ★ ⚠ same residue
ELN p.Gly413fs Likely pathogenic ★ same residue
ELN c.134-1G>A Likely pathogenic ★★ same type
ELN c.377-2A>G Pathogenic/Likely pathogenic ★★ same type
ELN c.643+1G>A Pathogenic/Likely pathogenic ★★ same type
ELN c.643+1G>C Likely pathogenic ★★ same type
ELN c.686-2A>G 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/eln-p-gly413arg (accessed [today's date]).

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