Is ELN p.Pro439= (c.1317C>T) pathogenic?

ELN p.Pro439= (c.1317C>T) is classified Benign/Likely benign in ELN (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-09-23). Ultra-rare (popmax 0.0825%, mid); Associated with cutis laxa, autosomal dominant 1.

What condition is associated with ELN p.Pro439= (c.1317C>T)?

ELN p.Pro439= (c.1317C>T) is associated with cutis laxa, autosomal dominant 1, supravalvular aortic stenosis (ClinVar).

How common is ELN p.Pro439= (c.1317C>T) in the general population?

ELN p.Pro439= (c.1317C>T) is ultra-rare (popmax 0.0825%, mid) (gnomAD).

How is Autosomal dominant cutis laxa inherited?

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

ELN p.Pro439=

c.1317C>T · rs201861098 · VCV360652

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0825%, mid)

Conditions

cutis laxa, autosomal dominant 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.90 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.19	GERP -2.2, phastCons 0.13
Overall
CADD	5.686	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0825% Middle Eastern · 5/6,062 alleles

Filtering AF 0.0324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.026%

Overall 0.00663% 107/1,613,792 alleles · ultra-rare exomes 86/1,461,568 · genomes 21/152,224 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0825%	1,212
African / African-American	0.0413%	2,420
South Asian	0.00659%	15,179
Remaining individualsnot grpmax-eligible	0.0064%	15,625
European (non-Finnish)	0.005%	20,001
East Asian	0.00223%	44,864
Finnishnot grpmax-eligible	0.00157%	63,710

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.Pro439=
Coding: c.1317C>T
MANE Select: NM_000501
dbSNP: rs201861098
Type: single nucleotide variant
Location: chr7:74056673 (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 p.Pro439Ser 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-pro439 (accessed [today's date]).

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