Is DEDD2 p.Leu42Gln (c.125T>A) pathogenic?

DEDD2 p.Leu42Gln (c.125T>A) is classified Uncertain significance in DEDD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-22). AlphaMissense: likely benign (0.2478); Absent from gnomAD v4.1.

How common is DEDD2 p.Leu42Gln (c.125T>A) in the general population?

DEDD2 p.Leu42Gln (c.125T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DEDD2 p.Leu42Gln (c.125T>A)?

AlphaMissense predicts likely benign (score 0.2478) — an in-silico prediction, not a clinical call.

DEDD2 p.Leu42Gln

c.125T>A · rs2513474572 · VCV3081259

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2478 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,598,258)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2478	likely benign
REVEL	0.322	indeterminate
SaProt	LLR -7.38	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.5, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 7,296 bp · p 0.6 · regional, not allelic
Overall
CADD	28.8	PHRED · no single calibrated threshold — expert panels disagree

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

No allele count reported in gnomAD v4.1 (AN 1,598,258). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DEDD2
Protein: p.Leu42Gln
Coding: c.125T>A
MANE Select: NM_133328
dbSNP: rs2513474572
Type: single nucleotide variant
Location: chr19:42216883 (GRCh38)
Gene constraint: LOEUF 1.12 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.80
Residue 42: the ded domain

Full DEDD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DEDD2 p.Ala103Glu Uncertain significance ★ ⚠ same type
DEDD2 p.Ala177Val Uncertain significance ★ ⚠ same type
DEDD2 p.Ala52Val Uncertain significance ★ ⚠ same type
DEDD2 p.Arg114Cys Uncertain significance ★ ⚠ same type
DEDD2 p.Arg131Cys Uncertain significance ★ ⚠ same type
DEDD2 p.Arg132Cys Uncertain significance ★ ⚠ same type
DEDD2 p.Arg132His Uncertain significance ★ ⚠ same type
DEDD2 p.Arg156Gln Uncertain significance ★ ⚠ same type

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/dedd2-p-leu42gln (accessed [today's date]).

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