Is ELP2 p.Arg413Ser (c.1239A>C) pathogenic?

ELP2 p.Arg413Ser (c.1239A>C) is classified Uncertain significance in ELP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-06-03). AlphaMissense: likely pathogenic (0.9981); Absent from gnomAD v4.1; Associated with intellectual developmental disorder, autosomal recessive 58.

What condition is associated with ELP2 p.Arg413Ser (c.1239A>C)?

ELP2 p.Arg413Ser (c.1239A>C) is associated with intellectual developmental disorder, autosomal recessive 58 (ClinVar).

How common is ELP2 p.Arg413Ser (c.1239A>C) in the general population?

ELP2 p.Arg413Ser (c.1239A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ELP2 p.Arg413Ser (c.1239A>C)?

AlphaMissense predicts likely pathogenic (score 0.9981) — an in-silico prediction, not a clinical call.

ELP2 p.Arg413Ser

c.1239A>C · rs2090517565 · VCV1030307

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9981 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

intellectual developmental disorder, autosomal recessive 58

Computational evidence

Protein change
AlphaMissense	0.9981	likely pathogenic · top 1% in ELP2
REVEL	0.618	indeterminate
SaProt	LLR -14.88	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.45	GERP -0.67, phastCons 0.94
Regional constraint	o/e 0.95	unconstrained · MANE · 45 kb · p 0.13 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ELP2
Protein: p.Arg413Ser
Coding: c.1239A>C
MANE Select: NM_018255
dbSNP: rs2090517565
Type: single nucleotide variant
Location: chr18:36154963 (GRCh38)
Gene constraint: LOEUF 0.869 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.49 · 4 PDB
Residue 413: 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.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-arg413ser (accessed [today's date]).

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