Is DEDD2 p.Gly65Ser (c.193G>A) pathogenic?

DEDD2 p.Gly65Ser (c.193G>A) is classified Uncertain significance in DEDD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-05). AlphaMissense: likely pathogenic (0.63); Absent from gnomAD v4.1.

How common is DEDD2 p.Gly65Ser (c.193G>A) in the general population?

DEDD2 p.Gly65Ser (c.193G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DEDD2 p.Gly65Ser (c.193G>A)?

AlphaMissense predicts likely pathogenic (score 0.63) — an in-silico prediction, not a clinical call.

DEDD2 p.Gly65Ser

c.193G>A · VCV3839245

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.63 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.63	likely pathogenic
REVEL	0.375	indeterminate
SaProt	LLR -13.10	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.5, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 7,296 bp · p 0.6 · regional, not allelic
Overall
CADD	27.3	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: DEDD2
Protein: p.Gly65Ser
Coding: c.193G>A
MANE Select: NM_133328
Type: single nucleotide variant
Location: chr19:42216815 (GRCh38)
Gene constraint: LOEUF 1.12 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.80
Residue 65: 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-gly65ser (accessed [today's date]).

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