Is ELP2 p.Asp813Val (c.2438A>T) pathogenic?

ELP2 p.Asp813Val (c.2438A>T) is classified Uncertain significance in ELP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-29). AlphaMissense: likely pathogenic (0.984); Very rare (popmax 0.00133%, afr); Associated with intellectual developmental disorder, autosomal recessive 58.

What condition is associated with ELP2 p.Asp813Val (c.2438A>T)?

ELP2 p.Asp813Val (c.2438A>T) is associated with intellectual developmental disorder, autosomal recessive 58 (ClinVar).

How common is ELP2 p.Asp813Val (c.2438A>T) in the general population?

ELP2 p.Asp813Val (c.2438A>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about ELP2 p.Asp813Val (c.2438A>T)?

AlphaMissense predicts likely pathogenic (score 0.984) — an in-silico prediction, not a clinical call.

ELP2 p.Asp813Val

c.2438A>T · rs2043974621 · VCV3065744

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.984 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual developmental disorder, autosomal recessive 58

Computational evidence

Protein change
AlphaMissense	0.984	likely pathogenic · top 7% in ELP2
REVEL	0.91	moderately pathogenic-leaning
SaProt	LLR -16.84	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 45 kb · p 0.13 · regional, not allelic
Overall
CADD	28.6	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

Grpmax group 0.00133% African / African-American · 1/75,068 alleles

Overall 0.000137% 2/1,461,850 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,510
African / African-Americangrpmax	0.00133%	75,068

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp813Val
Coding: c.2438A>T
MANE Select: NM_018255
dbSNP: rs2043974621
Type: single nucleotide variant
Location: chr18:36174598 (GRCh38)
Gene constraint: LOEUF 0.869 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.49 · 4 PDB
Residue 813: 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-asp813val (accessed [today's date]).

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