Is ELP1 p.Pro586= (c.1758T>G) pathogenic?

ELP1 p.Pro586= (c.1758T>G) is classified Benign/Likely benign in ELP1 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-04). Common (popmax 6.09%, sas) — too common for a highly-penetrant pathogenic allele; Associated with Riley-Day syndrome.

What condition is associated with ELP1 p.Pro586= (c.1758T>G)?

ELP1 p.Pro586= (c.1758T>G) is associated with Riley-Day syndrome (ClinVar).

How is Familial dysautonomia inherited?

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

ELP1 p.Pro586=

Q: How common is ELP1 p.Pro586= (c.1758T>G) in the general population?

ELP1 p.Pro586= (c.1758T>G) is common (popmax 6.09%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1758T>G · rs35054425 · VCV364572

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 6.09%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

Riley-Day syndrome

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 -0.018	GERP -3.2, phastCons 0.13
Overall
CADD	4.409	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.09% South Asian · 5,541/91,008 alleles

Filtering AF 5.95% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.9%

Overall 1.47% 23,786/1,613,206 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	6.09%	16
Middle Eastern	2.95%	34
Ashkenazi Jewishnot grpmax-eligible	2.29%	44
Remaining individualsnot grpmax-eligible	1.58%	63
European (non-Finnish)	1.33%	75
Admixed American	0.725%	138
African / African-American	0.205%	487
Finnishnot grpmax-eligible	0.141%	712
East Asian	0.0223%	4,488

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: ELP1
Protein: p.Pro586=
Coding: c.1758T>G
MANE Select: NM_003640
dbSNP: rs35054425
Type: single nucleotide variant
Location: chr9:108902935 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.31 · 5 PDB
Residue 586: a β-strand

Full ELP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Riley-Day syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial dysautonomia (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

ELP1 c.1361-1G>T Pathogenic/Likely pathogenic ★★ same condition
ELP1 c.1361-2A>G Pathogenic/Likely pathogenic ★★ same condition
ELP1 c.1461-1G>A Likely pathogenic ★★ same condition
ELP1 c.1644-1G>T Likely pathogenic ★★ same condition
ELP1 c.1644-2A>C Likely pathogenic ★★ same condition
ELP1 c.1854+1G>A Likely pathogenic ★★ same condition
ELP1 c.2015-2A>G Likely pathogenic ★★ same condition
ELP1 c.2204+6T>C 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/elp1-p-pro586 (accessed [today's date]).

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