Is DEDD p.Arg179Cys (c.535C>T) pathogenic?

DEDD p.Arg179Cys (c.535C>T) is classified Uncertain significance in DEDD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-05). AlphaMissense: ambiguous (0.3945); Ultra-rare (popmax 0.0413%, afr).

How common is DEDD p.Arg179Cys (c.535C>T) in the general population?

DEDD p.Arg179Cys (c.535C>T) is ultra-rare (popmax 0.0413%, afr) (gnomAD).

What do computational predictors say about DEDD p.Arg179Cys (c.535C>T)?

AlphaMissense predicts ambiguous (score 0.3945) — an in-silico prediction, not a clinical call.

DEDD p.Arg179Cys

c.535C>T · VCV3500745

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3945 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0413%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3945	ambiguous
REVEL	0.098	moderately benign-leaning
SaProt	LLR -10.21	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.2, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 1,945 bp · p 6.1e-05 · regional, not allelic
Overall
CADD	26.1	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 0.0413% African / African-American · 31/75,036 alleles

Filtering AF 0.0298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.026%

Overall 0.00279% 45/1,614,174 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0413%	2,421
Admixed American	0.00333%	30,012
Remaining individualsnot grpmax-eligible	0.0016%	62,510
Finnishnot grpmax-eligible	0.00156%	64,024
European (non-Finnish)	0.000847%	118,004

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.Arg179Cys
Coding: c.535C>T
MANE Select: NM_032998
Type: single nucleotide variant
Location: chr1:161123120 (GRCh38)
Gene constraint: LOEUF 0.255 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.90
Residue 179: the 'disordered' region

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.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
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-arg179cys (accessed [today's date]).

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