Is DHDDS p.Lys21Asn (c.63G>T) pathogenic?

DHDDS p.Lys21Asn (c.63G>T) is classified Uncertain significance in DHDDS (ClinVar, Single submitter, 2 submitters; last evaluated 2022-01-03). AlphaMissense: likely pathogenic (0.8063); Absent from gnomAD v4.1; Associated with developmental delay and seizures with or without movement abnormalities.

What condition is associated with DHDDS p.Lys21Asn (c.63G>T)?

DHDDS p.Lys21Asn (c.63G>T) is associated with developmental delay and seizures with or without movement abnormalities (ClinVar).

How common is DHDDS p.Lys21Asn (c.63G>T) in the general population?

DHDDS p.Lys21Asn (c.63G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DHDDS p.Lys21Asn (c.63G>T)?

AlphaMissense predicts likely pathogenic (score 0.8063) — an in-silico prediction, not a clinical call.

DHDDS p.Lys21Asn

c.63G>T · rs2124329750 · VCV1333480

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8063 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental delay and seizures with or without movement abnormalities

Computational evidence

Protein change
AlphaMissense	0.8063	likely pathogenic
REVEL	0.238	benign-leaning
SaProt	LLR -8.46	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	Δ0.89	donor gain · deltas
Pangolin	Δ0.69	gain · loss 0.47 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 9,886 bp · p 3.6e-06 · regional, not allelic
Overall
CADD	36.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DHDDS
Protein: p.Lys21Asn
Coding: c.63G>T
MANE Select: NM_205861
dbSNP: rs2124329750
Type: single nucleotide variant
Location: chr1:26433008 (GRCh38)
Gene constraint: LOEUF 0.536 · pLI 0.91 (gnomAD)
Structure: AlphaFold pLDDT 95.01 · 9 PDB

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

Disease context

developmental delay and seizures with or without movement abnormalities — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DHDDS c.658-2A>G Likely pathogenic ★★ same condition
DHDDS p.Arg205Gln Pathogenic ★★ same condition
DHDDS p.Arg211Gln Pathogenic ★★ same condition
DHDDS p.Arg37Cys Pathogenic ★★ same condition
DHDDS p.Arg37His Pathogenic/Likely pathogenic ★★ same condition
DHDDS p.Arg38His Pathogenic/Likely pathogenic ★★ same condition
DHDDS p.Lys42Glu Pathogenic ★★ ⚠ same condition
DHDDS p.Pro233Arg Pathogenic/Likely pathogenic ★★ same condition

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/dhdds-p-lys21asn (accessed [today's date]).

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