Is ELN p.Ala626Pro (c.1876G>C) pathogenic?

ELN p.Ala626Pro (c.1876G>C) is classified Uncertain significance in ELN (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-11-14). AlphaMissense: likely benign (0.2757); Very rare (popmax 0.00119%, sas); Associated with ELN-related disorder.

What condition is associated with ELN p.Ala626Pro (c.1876G>C)?

ELN p.Ala626Pro (c.1876G>C) is associated with ELN-related disorder (ClinVar).

How common is ELN p.Ala626Pro (c.1876G>C) in the general population?

ELN p.Ala626Pro (c.1876G>C) is very rare (popmax 0.00119%, sas) (gnomAD).

What do computational predictors say about ELN p.Ala626Pro (c.1876G>C)?

AlphaMissense predicts likely benign (score 0.2757) — an in-silico prediction, not a clinical call.

ELN p.Ala626Pro

c.1876G>C · rs781861907 · VCV3044269

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2757 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00119%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ELN-related disorder

Computational evidence

Protein change
AlphaMissense	0.2757	likely benign
REVEL	0.189	benign-leaning
SaProt	LLR -12.17	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.1	GERP -1.7
Regional constraint	o/e 0.91	unconstrained · MANE · 41 kb · p 0.005 · regional, not allelic
Overall
CADD	7.618	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A688P vs ClinVar A626P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00119% South Asian · 1/84,266 alleles

Overall 7.15e-05% 1/1,398,768 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.Ala626Pro
Coding: c.1876G>C
MANE Select: NM_000501
dbSNP: rs781861907
Type: single nucleotide variant
Location: chr7:74063327 (GRCh38)
Gene constraint: LOEUF 0.696 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 36.20
Residue 626: the 'disordered' region

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

Disease context

ELN-related disorder

Similar variants

ELN p.Ala626Thr Uncertain significance ★★ ⚠ same residue
ELN p.Ala626Val Uncertain significance ★ ⚠ same residue
ELN p.Ala626= Likely benign ★ same residue
ELN c.800-1G>A Pathogenic/Likely pathogenic ★★ same condition
ELN p.Arg541Ter Pathogenic ★★ same condition
ELN p.Gln442Ter Pathogenic ★★ same condition
ELN p.Met1Thr Pathogenic/Likely pathogenic ★★ same condition
ELN p.Ala447Thr 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-ala626pro (accessed [today's date]).

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