Is ELN p.Ala624= (c.1872C>T) pathogenic?

ELN p.Ala624= (c.1872C>T) is classified Likely benign in ELN (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-24). Ultra-rare (popmax 0.0436%, eas); Associated with supravalvular aortic stenosis.

What condition is associated with ELN p.Ala624= (c.1872C>T)?

ELN p.Ala624= (c.1872C>T) is associated with supravalvular aortic stenosis (ClinVar).

How common is ELN p.Ala624= (c.1872C>T) in the general population?

ELN p.Ala624= (c.1872C>T) is ultra-rare (popmax 0.0436%, eas) (gnomAD).

ELN p.Ala624=

c.1872C>T · rs781807182 · VCV509085

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0436%, eas)

Conditions

supravalvular aortic stenosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.5	GERP 1.1
Overall
CADD	6.314	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0436% East Asian · 18/41,312 alleles

Filtering AF 0.0281% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0232%

Overall 0.00735% 114/1,550,666 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0436%	2,295
Remaining individualsnot grpmax-eligible	0.00832%	12,024
European (non-Finnish)	0.0074%	13,510
Admixed American	0.00392%	25,508
African / African-American	0.00273%	36,622
South Asian	0.00237%	42,139

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.Ala624=
Coding: c.1872C>T
MANE Select: NM_000501
dbSNP: rs781807182
Type: single nucleotide variant
Location: chr7:74063323 (GRCh38)
Gene constraint: LOEUF 0.696 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 36.20
Residue 624: 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.Ala624Thr 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
ELN c.82+1G>A Pathogenic/Likely 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-ala624 (accessed [today's date]).

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