Is ELP2 p.Arg737Ter (c.2209C>T) pathogenic?

ELP2 p.Arg737Ter (c.2209C>T) is classified Likely pathogenic in ELP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-14). Very rare (popmax 0.00329%, sas); Associated with intellectual developmental disorder, autosomal recessive 58.

What condition is associated with ELP2 p.Arg737Ter (c.2209C>T)?

ELP2 p.Arg737Ter (c.2209C>T) is associated with intellectual developmental disorder, autosomal recessive 58 (ClinVar).

How common is ELP2 p.Arg737Ter (c.2209C>T) in the general population?

ELP2 p.Arg737Ter (c.2209C>T) is very rare (popmax 0.00329%, sas) (gnomAD).

ELP2 p.Arg737Ter

c.2209C>T · VCV4845862

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 0.00329%, sas)

Conditions

intellectual developmental disorder, autosomal recessive 58

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 20 of 22
Splicing
SpliceAI	Δ0.25	donor loss · deltas
Pangolin	Δ0.39	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -0.21	GERP -3.9
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 0.00329% South Asian · 3/91,090 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000929% 15/1,614,046 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,363
African / African-American	0.00267%	37,454
European (non-Finnish)	0.000847%	118,004

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.Arg737Ter
Coding: c.2209C>T
MANE Select: NM_018255
Type: single nucleotide variant
Location: chr18:36170195 (GRCh38)
Gene constraint: LOEUF 0.869 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.49 · 4 PDB

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.Arg333Ter Likely pathogenic ★ same condition
ELP2 p.Arg689Ter 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-arg737ter (accessed [today's date]).

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