Is ELP1 p.Gln489Pro (c.1466A>C) pathogenic?

ELP1 p.Gln489Pro (c.1466A>C) is classified Uncertain significance in ELP1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-11). AlphaMissense: likely benign (0.0739); Very rare (popmax 0.00102%, nfe); Associated with medulloblastoma.

What condition is associated with ELP1 p.Gln489Pro (c.1466A>C)?

ELP1 p.Gln489Pro (c.1466A>C) is associated with medulloblastoma, Riley-Day syndrome (ClinVar).

How common is ELP1 p.Gln489Pro (c.1466A>C) in the general population?

ELP1 p.Gln489Pro (c.1466A>C) is very rare (popmax 0.00102%, nfe) (gnomAD).

How is Medulloblastoma inherited?

Typically Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ELP1 p.Gln489Pro (c.1466A>C)?

AlphaMissense predicts likely benign (score 0.0739) — an in-silico prediction, not a clinical call.

ELP1 p.Gln489Pro

c.1466A>C · rs140229715 · VCV1357633

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0739 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

medulloblastoma

Computational evidence

Protein change
AlphaMissense	0.0739	likely benign
REVEL	0.064	moderately benign-leaning
SaProt	LLR -7.87	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP -3.2, phastCons 0.99
Regional constraint	o/e 0.97	unconstrained · MANE · 62 kb · p 0.26 · regional, not allelic
Overall
CADD	15.84	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 0.00102% European (non-Finnish) · 12/1,178,592 alleles

Filtering AF 0.000543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000429%

Overall 0.000744% 12/1,612,460 alleles · very rare

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.Gln489Pro
Coding: c.1466A>C
MANE Select: NM_003640
dbSNP: rs140229715
Type: single nucleotide variant
Location: chr9:108906480 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.31 · 5 PDB
Residue 489: a β-strand

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

Disease context

medulloblastoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Riley-Day syndrome

For Medulloblastoma (Orphanet):

Inheritance: Not applicable
Onset: All ages
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

ELP1 p.Gln489Ter Pathogenic/Likely pathogenic ★★ same residue
ELP1 p.Gln489_Phe490insTer Likely pathogenic ★ same residue
ELP1 p.Gln489= 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

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-gln489pro (accessed [today's date]).

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