Is DEDD p.Leu69Val (c.205T>G) pathogenic?

DEDD p.Leu69Val (c.205T>G) is classified Uncertain significance in DEDD (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-06). AlphaMissense: ambiguous (0.3971); Very rare (popmax 0.000508%, nfe).

How common is DEDD p.Leu69Val (c.205T>G) in the general population?

DEDD p.Leu69Val (c.205T>G) is very rare (popmax 0.000508%, nfe) (gnomAD).

What do computational predictors say about DEDD p.Leu69Val (c.205T>G)?

AlphaMissense predicts ambiguous (score 0.3971) — an in-silico prediction, not a clinical call.

DEDD p.Leu69Val

c.205T>G · rs1213021017 · VCV2303351

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3971 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000508%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3971	ambiguous
REVEL	0.321	indeterminate
SaProt	LLR -8.77	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.8	GERP -3.4
Regional constraint	o/e 0.76	unconstrained · MANE · 1,945 bp · p 6.1e-05 · regional, not allelic
Overall
CADD	17.47	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000508% European (non-Finnish) · 6/1,180,046 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,614,120 alleles · very rare

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: DEDD
Protein: p.Leu69Val
Coding: c.205T>G
MANE Select: NM_032998
dbSNP: rs1213021017
Type: single nucleotide variant
Location: chr1:161124258 (GRCh38)
Gene constraint: LOEUF 0.255 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.90
Residue 69: the ded domain

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

Similar variants

DEDD p.Arg124His Uncertain significance ★ ⚠ same type
DEDD p.Arg179Cys Uncertain significance ★ ⚠ same type
DEDD p.Arg196Lys Uncertain significance ★ ⚠ same type
DEDD p.Arg200Gln Uncertain significance ★ ⚠ same type
DEDD p.Arg228Cys Uncertain significance ★ ⚠ same type
DEDD p.Arg28His Uncertain significance ★ ⚠ same type
DEDD p.Arg58Cys Uncertain significance ★ ⚠ same type
DEDD p.Arg58His 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/dedd-p-leu69val (accessed [today's date]).

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