Is ELP2 p.Arg820fs (c.2460_2461del) pathogenic?

ELP2 p.Arg820fs (c.24602461del) is classified Likely pathogenic in ELP2 (ClinVar, No assertion criteria, 1 submitter). Very rare (popmax 0.000169%, nfe); Associated with Profound intellectual disability.

What condition is associated with ELP2 p.Arg820fs (c.2460_2461del)?

ELP2 p.Arg820fs (c.2460_2461del) is associated with Profound intellectual disability (ClinVar).

How common is ELP2 p.Arg820fs (c.2460_2461del) in the general population?

ELP2 p.Arg820fs (c.2460_2461del) is very rare (popmax 0.000169%, nfe) (gnomAD).

ELP2 p.Arg820fs

c.2460_2461del · rs1331690035 · VCV1012184

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Conditions

Profound intellectual disability

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (22 of 22) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.55	GERP -0.3, phastCons 0.99

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,020 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,834 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: ELP2
Protein: p.Arg820fs
Coding: c.2460_2461del
MANE Select: NM_018255
dbSNP: rs1331690035
Type: Microsatellite
Location: chr18:36174618 (GRCh38)
Gene constraint: LOEUF 0.869 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.49 · 4 PDB
Residue 820: a β-strand

Full ELP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Profound intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ELP2 p.Thr405Ile Likely pathogenic same condition
ELP2 p.Leu581fs Pathogenic/Likely pathogenic ★★ same type
ELP2 p.Ala825fs Uncertain significance ★ same type
ELP2 c.1275+11TTAT[5] Likely benign ★ same type

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/elp2-p-arg820fs (accessed [today's date]).

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