Is DEDD2 p.Arg171Trp (c.511C>T) pathogenic?

DEDD2 p.Arg171Trp (c.511C>T) is classified Uncertain significance in DEDD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-02). AlphaMissense: likely benign (0.182); Ultra-rare (popmax 0.0123%, amr).

How common is DEDD2 p.Arg171Trp (c.511C>T) in the general population?

DEDD2 p.Arg171Trp (c.511C>T) is ultra-rare (popmax 0.0123%, amr) (gnomAD).

What do computational predictors say about DEDD2 p.Arg171Trp (c.511C>T)?

AlphaMissense predicts likely benign (score 0.182) — an in-silico prediction, not a clinical call.

DEDD2 p.Arg171Trp

c.511C>T · rs762583652 · VCV2274946

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.182 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0123%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.182	likely benign
REVEL	0.279	benign-leaning
SaProt	LLR -9.94	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 7.5	GERP 1.6, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 7,296 bp · p 0.6 · regional, not allelic
Overall
CADD	32.0	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 0.0123% Admixed American · 7/57,026 alleles

Filtering AF 0.00569% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00407%

Overall 0.00389% 62/1,595,320 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0123%	8,147
Ashkenazi Jewishnot grpmax-eligible	0.00702%	14,245
East Asian	0.00456%	21,923
European (non-Finnish)	0.0041%	24,415
Remaining individualsnot grpmax-eligible	0.00324%	30,860
African / African-American	0.00135%	73,808

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.Arg171Trp
Coding: c.511C>T
MANE Select: NM_133328
dbSNP: rs762583652
Type: single nucleotide variant
Location: chr19:42209778 (GRCh38)
Gene constraint: LOEUF 1.12 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.80
Residue 171: the 'disordered' region

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

Similar variants

DEDD2 p.Arg171Gln 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-arg171trp (accessed [today's date]).

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