Is ELP2 p.Arg140Ter (c.418C>T) pathogenic?

ELP2 p.Arg140Ter (c.418C>T) is classified Pathogenic/Likely pathogenic in ELP2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-01). Ultra-rare (popmax 0.0233%, amr); Associated with intellectual developmental disorder, autosomal recessive 58.

What condition is associated with ELP2 p.Arg140Ter (c.418C>T)?

ELP2 p.Arg140Ter (c.418C>T) is associated with intellectual developmental disorder, autosomal recessive 58 (ClinVar).

How common is ELP2 p.Arg140Ter (c.418C>T) in the general population?

ELP2 p.Arg140Ter (c.418C>T) is ultra-rare (popmax 0.0233%, amr) (gnomAD).

ELP2 p.Arg140Ter

c.418C>T · VCV3336513

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0233%, amr)

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 4 of 22
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.11	GERP -5, phastCons 0.006
Overall
CADD	35.0	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 0.0233% Admixed American · 14/60,006 alleles

Filtering AF 0.0141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0112%

Overall 0.0031% 50/1,613,980 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0233%	4,286
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,802
Remaining individualsnot grpmax-eligible	0.0064%	15,627
South Asian	0.00329%	30,352
East Asian	0.00223%	44,868
European (non-Finnish)	0.00212%	47,200
African / African-American	0.00133%	74,988

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.Arg140Ter
Coding: c.418C>T
MANE Select: NM_018255
Type: single nucleotide variant
Location: chr18:36138399 (GRCh38)
Gene constraint: LOEUF 0.869 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.49 · 4 PDB
Residue 140: 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.Arg140Gln Uncertain significance ★ ⚠ same residue
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.Arg333Ter Likely pathogenic ★ same condition
ELP2 p.Arg689Ter Likely pathogenic ★ same condition
ELP2 p.Arg737Ter 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/elp2-p-arg140ter (accessed [today's date]).

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