Is ELN p.Pro161= (c.483C>T) pathogenic?

ELN p.Pro161= (c.483C>T) is classified Likely benign in ELN (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-09-07). Ultra-rare (popmax 0.0183%, amr); Associated with supravalvular aortic stenosis.

What condition is associated with ELN p.Pro161= (c.483C>T)?

ELN p.Pro161= (c.483C>T) is associated with supravalvular aortic stenosis (ClinVar).

How common is ELN p.Pro161= (c.483C>T) in the general population?

ELN p.Pro161= (c.483C>T) is ultra-rare (popmax 0.0183%, amr) (gnomAD).

ELN p.Pro161=

c.483C>T · rs150690195 · VCV700084

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0183%, amr)

Conditions

supravalvular aortic stenosis

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 -6.7	GERP -2.1
Overall
CADD	5.789	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0183% Admixed American · 11/60,028 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00785%

Overall 0.00818% 132/1,614,114 alleles · ultra-rare exomes 116/1,461,774 · genomes 16/152,340 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0183%	5,457
Middle Eastern	0.0165%	6,062
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,868
Remaining individualsnot grpmax-eligible	0.0096%	10,418
European (non-Finnish)	0.0089%	11,238
Finnishnot grpmax-eligible	0.00313%	31,972
African / African-American	0.00266%	37,530
East Asian	0.00223%	44,880
South Asian	0.0011%	91,086

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.Pro161=
Coding: c.483C>T
MANE Select: NM_000501
dbSNP: rs150690195
Type: single nucleotide variant
Location: chr7:74045235 (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

Similar variants

ELN p.Pro161Arg Uncertain significance ★ ⚠ same residue
ELN p.Pro161Leu Uncertain significance ★ ⚠ same residue
ELN p.Pro161His 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

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-pro161 (accessed [today's date]).

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