Is ELN p.Ala84Glu (c.251C>A) pathogenic?

ELN p.Ala84Glu (c.251C>A) is classified Uncertain significance in ELN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-21). AlphaMissense: ambiguous (0.5143); Absent from gnomAD v4.1.

How common is ELN p.Ala84Glu (c.251C>A) in the general population?

ELN p.Ala84Glu (c.251C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ELN p.Ala84Glu (c.251C>A)?

AlphaMissense predicts ambiguous (score 0.5143) — an in-silico prediction, not a clinical call.

ELN p.Ala84Glu

c.251C>A · rs1791498052 · VCV2441207

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5143 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5143	ambiguous
REVEL	0.214	benign-leaning
SaProt	LLR -7.77	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.51	GERP -0.079
Regional constraint	o/e 0.91	unconstrained · MANE · 41 kb · p 0.005 · regional, not allelic
Overall
CADD	15.02	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: ELN
Protein: p.Ala84Glu
Coding: c.251C>A
MANE Select: NM_000501
dbSNP: rs1791498052
Type: single nucleotide variant
Location: chr7:74042632 (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.Ala84Ser Uncertain significance ★★ ⚠ same residue
ELN p.Ala84Thr Uncertain significance ★★ ⚠ same residue
ELN p.Ala84= Likely benign ★ 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-ala84glu (accessed [today's date]).

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