Is DEDD2 p.Arg201Trp (c.601C>T) pathogenic?

DEDD2 p.Arg201Trp (c.601C>T) is classified Uncertain significance in DEDD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-31). AlphaMissense: likely pathogenic (0.9823); Very rare (popmax 0.00459%, eas).

How common is DEDD2 p.Arg201Trp (c.601C>T) in the general population?

DEDD2 p.Arg201Trp (c.601C>T) is very rare (popmax 0.00459%, eas) (gnomAD).

What do computational predictors say about DEDD2 p.Arg201Trp (c.601C>T)?

AlphaMissense predicts likely pathogenic (score 0.9823) — an in-silico prediction, not a clinical call.

DEDD2 p.Arg201Trp

c.601C>T · rs534601512 · VCV2467114

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9823 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00459%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9823	likely pathogenic
REVEL	0.348	indeterminate
SaProt	LLR -15.21	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 3.4	GERP -0.72, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 10 kb · p 9.8e-06 · regional, not allelic
Overall
CADD	33.0	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

Grpmax group 0.00459% East Asian · 2/43,564 alleles

Filtering AF 0.000761% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000285%

Overall 0.000754% 12/1,591,944 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00459%	21,782
Admixed American	0.00177%	56,340
African / African-American	0.00134%	74,368
European (non-Finnish)	0.000684%	146,114

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: DEDD2
Protein: p.Arg201Trp
Coding: c.601C>T
MANE Select: NM_133328
dbSNP: rs534601512
Type: single nucleotide variant
Location: chr19:42199818 (GRCh38)
Gene constraint: LOEUF 1.12 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.80

Full DEDD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DEDD2 p.Arg201Gln Uncertain significance ★ ⚠ same residue
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

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-arg201trp (accessed [today's date]).

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