Is ELP2 p.Arg333Ter (c.997C>T) pathogenic?

ELP2 p.Arg333Ter (c.997C>T) is classified Likely pathogenic in ELP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-17). Very rare (popmax 0.00401%, afr); Associated with intellectual developmental disorder, autosomal recessive 58.

What condition is associated with ELP2 p.Arg333Ter (c.997C>T)?

ELP2 p.Arg333Ter (c.997C>T) is associated with intellectual developmental disorder, autosomal recessive 58 (ClinVar).

How common is ELP2 p.Arg333Ter (c.997C>T) in the general population?

ELP2 p.Arg333Ter (c.997C>T) is very rare (popmax 0.00401%, afr) (gnomAD).

ELP2 p.Arg333Ter

c.997C>T · VCV4884198

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Conditions

intellectual developmental disorder, autosomal recessive 58

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 11 of 22
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 2.5, phastCons 1
Overall
CADD	44.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00401% African / African-American · 3/74,858 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000682% 11/1,613,768 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,953
South Asian	0.0011%	91,050
European (non-Finnish)	0.000593%	168,561

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.Arg333Ter
Coding: c.997C>T
MANE Select: NM_018255
Type: single nucleotide variant
Location: chr18:36146253 (GRCh38)
Gene constraint: LOEUF 0.869 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.49 · 4 PDB
Residue 333: a β-strand

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

Disease context

intellectual developmental disorder, autosomal recessive 58 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ELP2 p.Arg140Ter Pathogenic/Likely pathogenic ★★ same condition
ELP2 p.Arg462Gln Pathogenic/Likely pathogenic ★★ same condition
ELP2 p.Gln192Ter Pathogenic/Likely pathogenic ★★ same condition
ELP2 p.His206Arg Pathogenic/Likely pathogenic ★★ same condition
ELP2 p.Leu444Ser Uncertain significance ★★ ⚠ same condition
ELP2 p.Arg689Ter Likely pathogenic ★ same condition
ELP2 p.Arg737Ter Likely pathogenic ★ same condition
ELP2 p.Gln303Ter 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/elp2-p-arg333ter (accessed [today's date]).

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