Is ELN p.Ala81Asp (c.242C>A) pathogenic?

ELN p.Ala81Asp (c.242C>A) is classified Uncertain significance in ELN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-13). AlphaMissense: ambiguous (0.455); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ELN p.Ala81Asp (c.242C>A)?

ELN p.Ala81Asp (c.242C>A) is associated with Inborn genetic diseases (ClinVar).

How common is ELN p.Ala81Asp (c.242C>A) in the general population?

ELN p.Ala81Asp (c.242C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ELN p.Ala81Asp (c.242C>A)?

AlphaMissense predicts ambiguous (score 0.455) — an in-silico prediction, not a clinical call.

ELN p.Ala81Asp

c.242C>A · VCV4618437

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.455 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.455	ambiguous
REVEL	0.198	benign-leaning
SaProt	LLR -10.82	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP 5.7, phastCons 0.11
Regional constraint	o/e 0.91	unconstrained · MANE · 41 kb · p 0.005 · regional, not allelic
Overall
CADD	21.4	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.Ala81Asp
Coding: c.242C>A
MANE Select: NM_000501
Type: single nucleotide variant
Location: chr7:74042623 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ELN p.Ala81Pro Uncertain significance ★★ ⚠ same residue
ELN p.Ala81Thr Uncertain significance ★ ⚠ same residue
ELN p.Ala81Val Uncertain significance ★ ⚠ same residue
ELN c.800-3C>G Pathogenic ★★ same condition
ELN p.Gln131Ter Pathogenic ★★ same condition
ELN p.Ala187Thr Uncertain significance ★★ ⚠ same condition
ELN p.Ala363Val Uncertain significance ★★ ⚠ same condition
ELN p.Ala441Thr 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/eln-p-ala81asp (accessed [today's date]).

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