Is ELP1 p.Ser550Phe (c.1649C>T) pathogenic?

ELP1 p.Ser550Phe (c.1649C>T) is classified Uncertain significance in ELP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-28). AlphaMissense: likely benign (0.1376); Very rare (popmax 0.00834%, amr); Associated with Riley-Day syndrome.

What condition is associated with ELP1 p.Ser550Phe (c.1649C>T)?

ELP1 p.Ser550Phe (c.1649C>T) is associated with Riley-Day syndrome, medulloblastoma (ClinVar).

How common is ELP1 p.Ser550Phe (c.1649C>T) in the general population?

ELP1 p.Ser550Phe (c.1649C>T) is very rare (popmax 0.00834%, amr) (gnomAD).

How is Familial dysautonomia inherited?

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

What do computational predictors say about ELP1 p.Ser550Phe (c.1649C>T)?

AlphaMissense predicts likely benign (score 0.1376) — an in-silico prediction, not a clinical call.

ELP1 p.Ser550Phe

c.1649C>T · rs539141671 · VCV1800182

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1376 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00834%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Riley-Day syndrome

Computational evidence

Protein change
AlphaMissense	0.1376	likely benign
REVEL	0.304	indeterminate
SaProt	LLR -6.77	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 62 kb · p 0.26 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00834% Admixed American · 5/59,978 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.00062% 10/1,612,374 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00834%	11,996
East Asian	0.00669%	14,956
Remaining individualsnot grpmax-eligible	0.0016%	62,434
African / African-American	0.00134%	74,866

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.Ser550Phe
Coding: c.1649C>T
MANE Select: NM_003640
dbSNP: rs539141671
Type: single nucleotide variant
Location: chr9:108903664 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.31 · 5 PDB
Residue 550: 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

Also linked: medulloblastoma

For Familial dysautonomia (Orphanet):

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

Similar variants

ELP1 p.Ser550Cys Uncertain significance ★ ⚠ same residue
ELP1 p.Ser550= Likely benign ★ 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

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-ser550phe (accessed [today's date]).

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