Is DEDD p.Arg58Cys (c.172C>T) pathogenic?

DEDD p.Arg58Cys (c.172C>T) is classified Uncertain significance in DEDD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-18). AlphaMissense: likely pathogenic (0.9294); Very rare (popmax 0.00133%, afr).

How common is DEDD p.Arg58Cys (c.172C>T) in the general population?

DEDD p.Arg58Cys (c.172C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about DEDD p.Arg58Cys (c.172C>T)?

AlphaMissense predicts likely pathogenic (score 0.9294) — an in-silico prediction, not a clinical call.

DEDD p.Arg58Cys

c.172C>T · VCV3271429

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9294 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9294	likely pathogenic
REVEL	0.201	benign-leaning
SaProt	LLR -11.38	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 1,945 bp · p 6.1e-05 · regional, not allelic
Overall
CADD	32.0	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 0.00133% African / African-American · 1/75,046 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000342% 5/1,461,866 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,046
South Asian	0.0011%	91,082
European (non-Finnish)	0.000254%	393,345

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.Arg58Cys
Coding: c.172C>T
MANE Select: NM_032998
Type: single nucleotide variant
Location: chr1:161124291 (GRCh38)
Gene constraint: LOEUF 0.255 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.90
Residue 58: the ded domain

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

Similar variants

DEDD p.Arg58His Uncertain significance ★ ⚠ same residue
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.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-arg58cys (accessed [today's date]).

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