Is ELN p.Ala629Thr (c.1885G>A) pathogenic?

ELN p.Ala629Thr (c.1885G>A) is classified Uncertain significance in ELN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-22). AlphaMissense: likely benign (0.2717); Ultra-rare (popmax 0.0109%, afr); Associated with supravalvular aortic stenosis.

What condition is associated with ELN p.Ala629Thr (c.1885G>A)?

ELN p.Ala629Thr (c.1885G>A) is associated with supravalvular aortic stenosis (ClinVar).

How common is ELN p.Ala629Thr (c.1885G>A) in the general population?

ELN p.Ala629Thr (c.1885G>A) is ultra-rare (popmax 0.0109%, afr) (gnomAD).

What do computational predictors say about ELN p.Ala629Thr (c.1885G>A)?

AlphaMissense predicts likely benign (score 0.2717) — an in-silico prediction, not a clinical call.

ELN p.Ala629Thr

c.1885G>A · VCV3373547

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2717 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0109%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

supravalvular aortic stenosis

Computational evidence

Protein change
AlphaMissense	0.2717	likely benign
REVEL	0.171	moderately benign-leaning
SaProt	LLR -11.60	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 11	GERP 5, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 41 kb · p 0.005 · regional, not allelic
Overall
CADD	23.7	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 A691T vs ClinVar A629T) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0109% African / African-American · 8/73,390 alleles

Filtering AF 0.00537% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00387%

Overall 0.00168% 26/1,550,532 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0109%	9,174
East Asian	0.00242%	41,256
European (non-Finnish)	0.00148%	67,538

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.Ala629Thr
Coding: c.1885G>A
MANE Select: NM_000501
Type: single nucleotide variant
Location: chr7:74063336 (GRCh38)
Gene constraint: LOEUF 0.696 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 36.20
Residue 629: the 'disordered' region

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

Disease context

supravalvular aortic stenosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ELN p.Ala629_Ala630del Uncertain significance ★ same residue
ELN p.Ala629_Ala634dup Uncertain significance ★ same residue
ELN c.377-2A>G Pathogenic/Likely pathogenic ★★ same condition
ELN c.643+1G>C Likely pathogenic ★★ same condition
ELN c.686-2A>G Likely pathogenic ★★ same condition
ELN c.800-1G>A Pathogenic/Likely pathogenic ★★ same condition
ELN c.800-2A>G Pathogenic ★★ same condition
ELN c.800-3C>G Pathogenic ★★ 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-ala629thr (accessed [today's date]).

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