Is DEDD2 p.Phe30Tyr (c.89T>A) pathogenic?

DEDD2 p.Phe30Tyr (c.89T>A) is classified Uncertain significance in DEDD2 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-03-15). AlphaMissense: likely pathogenic (0.7008); Rare (popmax 0.122%, afr).

How common is DEDD2 p.Phe30Tyr (c.89T>A) in the general population?

DEDD2 p.Phe30Tyr (c.89T>A) is rare (popmax 0.122%, afr) (gnomAD).

What do computational predictors say about DEDD2 p.Phe30Tyr (c.89T>A)?

AlphaMissense predicts likely pathogenic (score 0.7008) — an in-silico prediction, not a clinical call.

DEDD2 p.Phe30Tyr

c.89T>A · VCV3271432

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7008 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.122%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7008	likely pathogenic
REVEL	0.429	indeterminate
SaProt	LLR -7.72	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.2	GERP 1.5, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 7,296 bp · p 0.6 · regional, not allelic
Overall
CADD	27.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.122% African / African-American · 91/74,560 alleles

Filtering AF 0.102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0942%

Overall 0.00793% 127/1,600,694 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.122%	819
Middle Eastern	0.0496%	2,017
Admixed American	0.0307%	3,260
Remaining individualsnot grpmax-eligible	0.00968%	10,334
European (non-Finnish)	0.000767%	130,462

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.Phe30Tyr
Coding: c.89T>A
MANE Select: NM_133328
Type: single nucleotide variant
Location: chr19:42216919 (GRCh38)
Gene constraint: LOEUF 1.12 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.80
Residue 30: the ded domain

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

Similar variants

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
DEDD2 p.Arg156Gln 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-phe30tyr (accessed [today's date]).

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