Is ELN p.Ala531Phe (c.1591_1592delinsTT) pathogenic?

ELN p.Ala531Phe (c.15911592delinsTT) is classified Uncertain significance in ELN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-05-12). No gnomAD frequency available for this variant; Associated with Williams syndrome.

What condition is associated with ELN p.Ala531Phe (c.1591_1592delinsTT)?

ELN p.Ala531Phe (c.1591_1592delinsTT) is associated with Williams syndrome, cutis laxa, autosomal dominant 1, supravalvular aortic stenosis (ClinVar).

How common is ELN p.Ala531Phe (c.1591_1592delinsTT) in the general population?

ELN p.Ala531Phe (c.1591_1592delinsTT) is no gnomAD frequency available for this variant (gnomAD).

ELN p.Ala531Phe

c.1591_1592delinsTT · rs863223529 · VCV213198

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Williams syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.4	GERP 5.5, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 41 kb · p 0.005 · regional, not allelic

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.Ala531Phe
Coding: c.1591_1592delinsTT
MANE Select: NM_000501
dbSNP: rs863223529
Type: Indel
Location: chr7:74060154 (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

Williams syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cutis laxa, autosomal dominant 1 supravalvular aortic stenosis

Similar variants

ELN p.Ala531Thr Uncertain significance ★★ ⚠ same residue
ELN p.Ala531fs Pathogenic ★ same residue
ELN c.643+1_643+2delinsAG Pathogenic ★ same condition
ELN p.Ala185fs 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

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-ala531phe (accessed [today's date]).

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