Is ELN p.Gly607= (c.1821G>C) pathogenic?

ELN p.Gly607= (c.1821G>C) is classified Benign/Likely benign in ELN (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-06). Rare (popmax 0.351%, afr); Associated with cutis laxa, autosomal dominant 1.

What condition is associated with ELN p.Gly607= (c.1821G>C)?

ELN p.Gly607= (c.1821G>C) is associated with cutis laxa, autosomal dominant 1, supravalvular aortic stenosis (ClinVar).

How common is ELN p.Gly607= (c.1821G>C) in the general population?

ELN p.Gly607= (c.1821G>C) is rare (popmax 0.351%, afr) (gnomAD).

How is Autosomal dominant cutis laxa inherited?

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

ELN p.Gly607=

c.1821G>C · rs144835575 · VCV360657

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.351%, afr)

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.39	GERP -4.4
Overall
CADD	0.887	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.351% African / African-American · 263/74,934 alleles

Filtering AF 0.316% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.303%

Overall 0.0191% 308/1,609,750 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.351%	285
Middle Eastern	0.0495%	2,019
Remaining individualsnot grpmax-eligible	0.0385%	2,598
Admixed American	0.0202%	4,946
South Asian	0.00448%	22,333
European (non-Finnish)	0.00017%	589,484

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.Gly607=
Coding: c.1821G>C
MANE Select: NM_000501
dbSNP: rs144835575
Type: single nucleotide variant
Location: chr7:74063187 (GRCh38)
Gene constraint: LOEUF 0.696 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 36.20
Residue 607: a modified residue (4-hydroxyproline; partial)

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.Gly607Arg Uncertain significance ★★ ⚠ same residue
ELN p.Gly607Ala 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

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-gly607 (accessed [today's date]).

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