Is ELN p.Ala296Thr (c.886G>A) pathogenic?

ELN p.Ala296Thr (c.886G>A) is classified Benign/Likely benign in ELN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-17). AlphaMissense: likely benign (0.1873); Rare (popmax 0.256%, eas); Associated with cutis laxa, autosomal dominant 1.

What condition is associated with ELN p.Ala296Thr (c.886G>A)?

ELN p.Ala296Thr (c.886G>A) is associated with cutis laxa, autosomal dominant 1, supravalvular aortic stenosis (ClinVar).

How common is ELN p.Ala296Thr (c.886G>A) in the general population?

ELN p.Ala296Thr (c.886G>A) is rare (popmax 0.256%, eas) (gnomAD).

How is Autosomal dominant cutis laxa inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ELN p.Ala296Thr (c.886G>A)?

AlphaMissense predicts likely benign (score 0.1873) — an in-silico prediction, not a clinical call.

ELN p.Ala296Thr

c.886G>A · rs782335529 · VCV360639

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1873 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.256%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cutis laxa, autosomal dominant 1

Computational evidence

Protein change
AlphaMissense	0.1873	likely benign
REVEL	0.024	moderately benign-leaning
SaProt	LLR -6.88	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.5	GERP 4.9, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 41 kb · p 0.005 · regional, not allelic
Overall
CADD	21.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.256% East Asian · 115/44,878 alleles

Filtering AF 0.218% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.204%

Overall 0.00818% 132/1,614,236 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.256%	390
South Asian	0.00439%	22,772
Remaining individualsnot grpmax-eligible	0.0032%	31,254
Finnishnot grpmax-eligible	0.00312%	32,021
African / African-American	0.00133%	75,070
European (non-Finnish)	0.000678%	147,505

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.Ala296Thr
Coding: c.886G>A
MANE Select: NM_000501
dbSNP: rs782335529
Type: single nucleotide variant
Location: chr7:74051836 (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

cutis laxa, autosomal dominant 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: supravalvular aortic stenosis

For Autosomal dominant cutis laxa (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy, Neonatal

Similar variants

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
ELN c.889+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-ala296thr (accessed [today's date]).

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