Is DEDD2 p.Pro153Thr (c.457C>A) pathogenic?

DEDD2 p.Pro153Thr (c.457C>A) is classified Uncertain significance in DEDD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-06). AlphaMissense: likely benign (0.1025); Rare (popmax 0.477%, mid).

How common is DEDD2 p.Pro153Thr (c.457C>A) in the general population?

DEDD2 p.Pro153Thr (c.457C>A) is rare (popmax 0.477%, mid) (gnomAD).

What do computational predictors say about DEDD2 p.Pro153Thr (c.457C>A)?

AlphaMissense predicts likely benign (score 0.1025) — an in-silico prediction, not a clinical call.

DEDD2 p.Pro153Thr

c.457C>A · VCV4239140

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1025 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.477%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1025	likely benign
REVEL	0.062	moderately benign-leaning
SaProt	LLR -8.04	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 6.6	GERP 1.6, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 7,296 bp · p 0.6 · regional, not allelic
Overall
CADD	20.6	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 0.477% Middle Eastern · 27/5,658 alleles

Filtering AF 0.337% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.29%

Overall 0.0335% 515/1,537,356 alleles · rare exomes 473/1,385,188 · genomes 42/152,168 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.477%	210
Remaining individualsnot grpmax-eligible	0.102%	984
African / African-American	0.0849%	1,178
Admixed American	0.0479%	2,089
European (non-Finnish)	0.0285%	3,507
South Asian	0.0169%	5,906
Finnishnot grpmax-eligible	0.00653%	15,305
Ashkenazi Jewishnot grpmax-eligible	0.00391%	25,582

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.Pro153Thr
Coding: c.457C>A
MANE Select: NM_133328
Type: single nucleotide variant
Location: chr19:42209832 (GRCh38)
Gene constraint: LOEUF 1.12 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.80
Residue 153: the 'disordered' region

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

Similar variants

DEDD2 p.Pro153Ala Uncertain significance ★ ⚠ same residue
DEDD2 p.Pro153Arg Uncertain significance ★ ⚠ same residue
DEDD2 p.Pro153Leu 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

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-pro153thr (accessed [today's date]).

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