Is DHDDS p.Asn18Lys (c.54C>A) pathogenic?

DHDDS p.Asn18Lys (c.54C>A) is classified Uncertain significance in DHDDS (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-02). AlphaMissense: likely benign (0.2898); Absent from gnomAD v4.1.

How common is DHDDS p.Asn18Lys (c.54C>A) in the general population?

DHDDS p.Asn18Lys (c.54C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DHDDS p.Asn18Lys (c.54C>A)?

AlphaMissense predicts likely benign (score 0.2898) — an in-silico prediction, not a clinical call.

DHDDS p.Asn18Lys

c.54C>A · rs2524405537 · VCV2501404

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2898 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2898	likely benign
REVEL	0.094	moderately benign-leaning
SaProt	LLR -7.19	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 0.2	GERP -2.1, phastCons 0.98
Regional constraint	o/e 0.58	unconstrained · MANE · 9,886 bp · p 3.6e-06 · regional, not allelic
Overall
CADD	15.41	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

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.Asn18Lys
Coding: c.54C>A
MANE Select: NM_205861
dbSNP: rs2524405537
Type: single nucleotide variant
Location: chr1:26432999 (GRCh38)
Gene constraint: LOEUF 0.536 · pLI 0.91 (gnomAD)
Structure: AlphaFold pLDDT 95.01 · 9 PDB
Residue 18: an α-helix

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

Similar variants

DHDDS p.Asn18Ser Uncertain significance ★★ ⚠ same residue
DHDDS c.658-2A>G Likely pathogenic ★★ same type
DHDDS p.Arg205Gln Pathogenic ★★ same type
DHDDS p.Arg211Gln Pathogenic ★★ same type
DHDDS p.Arg37Cys Pathogenic ★★ same type
DHDDS p.Arg37His Pathogenic/Likely pathogenic ★★ same type
DHDDS p.Arg37Ser Pathogenic ★★ same type
DHDDS p.Arg38His Pathogenic/Likely pathogenic ★★ 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/dhdds-p-asn18lys (accessed [today's date]).

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