Is ELN p.Ala185fs (c.554_555delinsA) pathogenic?

ELN p.Ala185fs (c.554555delinsA) is classified Pathogenic in ELN (ClinVar, Single submitter, 1 submitter; last evaluated 2020-12-13). Absent from gnomAD; Associated with supravalvular aortic stenosis.

What condition is associated with ELN p.Ala185fs (c.554_555delinsA)?

ELN p.Ala185fs (c.554_555delinsA) is associated with supravalvular aortic stenosis (ClinVar).

How common is ELN p.Ala185fs (c.554_555delinsA) in the general population?

ELN p.Ala185fs (c.554_555delinsA) is absent from gnomAD (gnomAD).

ELN p.Ala185fs

c.554_555delinsA · rs2485343633 · VCV3010196

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

supravalvular aortic stenosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 11 of 33
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.5	GERP 5.8, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ELN
Protein: p.Ala185fs
Coding: c.554_555delinsA
MANE Select: NM_000501
dbSNP: rs2485343633
Type: Indel
Location: chr7:74046200 (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

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

Similar variants

ELN p.Ala185Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
ELN p.Ala531Phe Uncertain significance ★★ same condition
ELN c.643+1_643+2delinsAG Pathogenic ★ same condition
ELN p.Gly135Ter Pathogenic ★ same condition
ELN c.1315+17_1315+18delinsTT Uncertain significance ★ same condition
ELN c.2092_2131+762delinsC Uncertain significance ★ same condition
ELN p.Ala575Cys Uncertain significance ★ same condition
ELN p.Gly581Gln Conflicting classifications of pathogenicity ★ 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-ala185fs (accessed [today's date]).

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