Is DEDD p.Arg228Cys (c.682C>T) pathogenic?

DEDD p.Arg228Cys (c.682C>T) is classified Uncertain significance in DEDD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-06). AlphaMissense: likely benign (0.2678); Very rare (popmax 0.00267%, afr).

How common is DEDD p.Arg228Cys (c.682C>T) in the general population?

DEDD p.Arg228Cys (c.682C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about DEDD p.Arg228Cys (c.682C>T)?

AlphaMissense predicts likely benign (score 0.2678) — an in-silico prediction, not a clinical call.

DEDD p.Arg228Cys

c.682C>T · rs150690350 · VCV2481115

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2678 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2678	likely benign
REVEL	0.291	indeterminate
SaProt	LLR -9.62	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.7, phastCons 1
Regional constraint	o/e 0.38	unconstrained · MANE · 366 bp · p 2.7e-14 · regional, not allelic
Overall
CADD	27.9	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 0.00267% African / African-American · 2/74,918 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000558% 9/1,614,064 alleles · very rare exomes 7/1,461,894 · genomes 2/152,170 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,245
African / African-Americangrpmax	0.00267%	37,459
East Asian	0.00223%	44,898
South Asian	0.0011%	91,084
European (non-Finnish)	0.000254%	393,349

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg228Cys
Coding: c.682C>T
MANE Select: NM_032998
dbSNP: rs150690350
Type: single nucleotide variant
Location: chr1:161122422 (GRCh38)
Gene constraint: LOEUF 0.255 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.90

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.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-arg228cys (accessed [today's date]).

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