Is ELN p.Val559Ile (c.1675G>A) pathogenic?

ELN p.Val559Ile (c.1675G>A) is classified Conflicting classifications of pathogenicity in ELN (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-01-07). AlphaMissense: likely benign (0.104); Ultra-rare (popmax 0.0401%, eas); Associated with Inborn genetic diseases.

What condition is associated with ELN p.Val559Ile (c.1675G>A)?

ELN p.Val559Ile (c.1675G>A) is associated with Inborn genetic diseases, cutis laxa, autosomal dominant 1, supravalvular aortic stenosis (ClinVar).

How common is ELN p.Val559Ile (c.1675G>A) in the general population?

ELN p.Val559Ile (c.1675G>A) is ultra-rare (popmax 0.0401%, eas) (gnomAD).

What do computational predictors say about ELN p.Val559Ile (c.1675G>A)?

AlphaMissense predicts likely benign (score 0.104) — an in-silico prediction, not a clinical call.

ELN p.Val559Ile

c.1675G>A · rs560081099 · VCV524219

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.104 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0401%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.104	likely benign
REVEL	0.025	moderately benign-leaning
SaProt	LLR -8.97	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.2	GERP 1.6, phastCons 0.69
Regional constraint	o/e 0.91	unconstrained · MANE · 41 kb · p 0.005 · regional, not allelic
Overall
CADD	6.759	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 V588I vs ClinVar V559I) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0401% East Asian · 18/44,868 alleles

Filtering AF 0.0259% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0214%

Overall 0.00601% 97/1,614,162 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0401%	2,493
South Asian	0.0263%	3,795
Admixed American	0.0167%	6,003
Remaining individualsnot grpmax-eligible	0.0128%	7,814
African / African-American	0.00933%	10,721
European (non-Finnish)	0.00246%	40,690
Finnishnot grpmax-eligible	0.00156%	64,040

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.Val559Ile
Coding: c.1675G>A
dbSNP: rs560081099
Type: single nucleotide variant
Location: chr7:74060429 (GRCh38)

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

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

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-val559ile (accessed [today's date]).

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