Is ELN p.Val423= (c.1269C>T) pathogenic?

ELN p.Val423= (c.1269C>T) is classified Benign/Likely benign in ELN (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-01-24). Rare (popmax 0.702%, afr); Associated with supravalvular aortic stenosis.

What condition is associated with ELN p.Val423= (c.1269C>T)?

ELN p.Val423= (c.1269C>T) is associated with supravalvular aortic stenosis, cutis laxa, autosomal dominant 1 (ClinVar).

How common is ELN p.Val423= (c.1269C>T) in the general population?

ELN p.Val423= (c.1269C>T) is rare (popmax 0.702%, afr) (gnomAD).

ELN p.Val423=

c.1269C>T · rs61734583 · VCV195473

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

rare (popmax 0.702%, afr)

Conditions

supravalvular aortic stenosis

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>G here scores Δ0.40 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.13	GERP -1.7, phastCons 0.04
Overall
CADD	2.061	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.702% African / African-American · 526/74,912 alleles

Filtering AF 0.652% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.633%

Overall 0.0359% 579/1,613,340 alleles · rare exomes 299/1,461,296 · genomes 280/152,044 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.702%	142
Middle Eastern	0.066%	1,514
Remaining individualsnot grpmax-eligible	0.0368%	2,716
Admixed American	0.0217%	4,611
South Asian	0.00329%	30,352
European (non-Finnish)	0.000848%	117,957

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.Val423=
Coding: c.1269C>T
MANE Select: NM_000501
dbSNP: rs61734583
Type: single nucleotide variant
Location: chr7:74056389 (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

supravalvular aortic stenosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cutis laxa, autosomal dominant 1

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-val423 (accessed [today's date]).

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