Is ELP1 p.Pro1212= (c.3636G>A) pathogenic?

ELP1 p.Pro1212= (c.3636G>A) is classified Likely benign in ELP1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-02). Very rare (popmax 0.00333%, amr); Associated with Riley-Day syndrome.

What condition is associated with ELP1 p.Pro1212= (c.3636G>A)?

ELP1 p.Pro1212= (c.3636G>A) is associated with Riley-Day syndrome (ClinVar).

How common is ELP1 p.Pro1212= (c.3636G>A) in the general population?

ELP1 p.Pro1212= (c.3636G>A) is very rare (popmax 0.00333%, amr) (gnomAD).

How is Familial dysautonomia inherited?

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

ELP1 p.Pro1212=

c.3636G>A · rs780520998 · VCV387789

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

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 -20	GERP -3.9
Overall
CADD	0.023	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,002 alleles

Filtering AF 0.00247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00217%

Overall 0.00266% 43/1,614,022 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,001
European (non-Finnish)	0.00331%	30,255
Remaining individualsnot grpmax-eligible	0.0016%	62,478
African / African-American	0.00133%	74,952

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.Pro1212=
Coding: c.3636G>A
MANE Select: NM_003640
dbSNP: rs780520998
Type: single nucleotide variant
Location: chr9:108878687 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.31 · 5 PDB
Residue 1212: the 'mediates dimerization' region

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 p.Pro1212Leu Uncertain significance ★ ⚠ same residue
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

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-pro1212 (accessed [today's date]).

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