Is DEDD2 p.Arg172Gln (c.515G>A) pathogenic?

DEDD2 p.Arg172Gln (c.515G>A) is classified Uncertain significance in DEDD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-12). AlphaMissense: likely benign (0.0641); Ultra-rare (popmax 0.0114%, eas).

How common is DEDD2 p.Arg172Gln (c.515G>A) in the general population?

DEDD2 p.Arg172Gln (c.515G>A) is ultra-rare (popmax 0.0114%, eas) (gnomAD).

What do computational predictors say about DEDD2 p.Arg172Gln (c.515G>A)?

AlphaMissense predicts likely benign (score 0.0641) — an in-silico prediction, not a clinical call.

DEDD2 p.Arg172Gln

c.515G>A · VCV4010599

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0641 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0114%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0641	likely benign
REVEL	0.014	strongly benign-leaning
SaProt	LLR -7.96	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 0.49	GERP 0.48, phastCons 0.011
Regional constraint	o/e 1.03	unconstrained · MANE · 7,296 bp · p 0.6 · regional, not allelic
Overall
CADD	22.0	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 0.0114% East Asian · 5/43,948 alleles

Filtering AF 0.00442% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00291%

Overall 0.00163% 26/1,597,700 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0114%	8,790
Remaining individualsnot grpmax-eligible	0.0113%	8,832
African / African-American	0.00676%	14,791
South Asian	0.00112%	89,472
European (non-Finnish)	0.000682%	146,642

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.Arg172Gln
Coding: c.515G>A
MANE Select: NM_133328
Type: single nucleotide variant
Location: chr19:42209774 (GRCh38)
Gene constraint: LOEUF 1.12 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.80
Residue 172: the 'disordered' region

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

Similar variants

DEDD2 p.Arg172Trp 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-arg172gln (accessed [today's date]).

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