Is DEDD p.Arg28His (c.83G>A) pathogenic?

DEDD p.Arg28His (c.83G>A) is classified Uncertain significance in DEDD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-28). AlphaMissense: likely benign (0.1165); Rare (popmax 0.165%, mid).

How common is DEDD p.Arg28His (c.83G>A) in the general population?

DEDD p.Arg28His (c.83G>A) is rare (popmax 0.165%, mid) (gnomAD).

What do computational predictors say about DEDD p.Arg28His (c.83G>A)?

AlphaMissense predicts likely benign (score 0.1165) — an in-silico prediction, not a clinical call.

DEDD p.Arg28His

c.83G>A · rs139003041 · VCV3081257

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1165 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1165	likely benign
REVEL	0.112	moderately benign-leaning
SaProt	LLR -4.63	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 0.61, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 1,945 bp · p 6.1e-05 · regional, not allelic
Overall
CADD	24.0	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

Grpmax group 0.165% Middle Eastern · 10/6,062 alleles

Filtering AF 0.0895% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0681%

Overall 0.0252% 407/1,614,130 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.165%	606
Remaining individualsnot grpmax-eligible	0.032%	3,125
European (non-Finnish)	0.0292%	3,420
Admixed American	0.0167%	6,003
African / African-American	0.016%	6,256
South Asian	0.011%	9,109

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.Arg28His
Coding: c.83G>A
MANE Select: NM_032998
dbSNP: rs139003041
Type: single nucleotide variant
Location: chr1:161124380 (GRCh38)
Gene constraint: LOEUF 0.255 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.90
Residue 28: 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.Arg58Cys Uncertain significance ★ ⚠ same type
DEDD p.Arg58His Uncertain significance ★ ⚠ same type
DEDD p.Arg65His 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-arg28his (accessed [today's date]).

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