Is ELN p.Ala636Thr (c.1906G>A) pathogenic?

ELN p.Ala636Thr (c.1906G>A) is classified Uncertain significance in ELN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-06). AlphaMissense: ambiguous (0.4179); Very rare (popmax 0.00119%, sas); Associated with Inborn genetic diseases.

What condition is associated with ELN p.Ala636Thr (c.1906G>A)?

ELN p.Ala636Thr (c.1906G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ELN p.Ala636Thr (c.1906G>A) in the general population?

ELN p.Ala636Thr (c.1906G>A) is very rare (popmax 0.00119%, sas) (gnomAD).

What do computational predictors say about ELN p.Ala636Thr (c.1906G>A)?

AlphaMissense predicts ambiguous (score 0.4179) — an in-silico prediction, not a clinical call.

ELN p.Ala636Thr

c.1906G>A · VCV3275192

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4179 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00119%, sas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4179	ambiguous
REVEL	0.128	moderately benign-leaning
SaProt	LLR -11.93	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 6.1, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 41 kb · p 0.005 · regional, not allelic
Overall
CADD	22.9	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 A698T vs ClinVar A636T) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00119% South Asian · 1/84,208 alleles

Overall 7.17e-05% 1/1,395,462 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.Ala636Thr
Coding: c.1906G>A
MANE Select: NM_000501
Type: single nucleotide variant
Location: chr7:74063357 (GRCh38)
Gene constraint: LOEUF 0.696 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 36.20
Residue 636: the 'disordered' region

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.Ala636= Likely benign ★ 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
ELN p.Ala468Thr Uncertain significance ★★ ⚠ same condition
ELN p.Ala525Thr 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-ala636thr (accessed [today's date]).

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