Is DHDDS p.Asn146Lys (c.438C>G) pathogenic?

DHDDS p.Asn146Lys (c.438C>G) is classified Uncertain significance in DHDDS (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-04). AlphaMissense: likely benign (0.1729); Absent from gnomAD v4.1.

How common is DHDDS p.Asn146Lys (c.438C>G) in the general population?

DHDDS p.Asn146Lys (c.438C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DHDDS p.Asn146Lys (c.438C>G)?

AlphaMissense predicts likely benign (score 0.1729) — an in-silico prediction, not a clinical call.

DHDDS p.Asn146Lys

c.438C>G · rs2124426386 · VCV1686618

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1729 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1729	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -7.18	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 2.7	GERP -0.91, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 26 kb · p 0.063 · regional, not allelic
Overall
CADD	18.08	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.Asn146Lys
Coding: c.438C>G
MANE Select: NM_205861
dbSNP: rs2124426386
Type: single nucleotide variant
Location: chr1:26446430 (GRCh38)
Gene constraint: LOEUF 0.536 · pLI 0.91 (gnomAD)
Structure: AlphaFold pLDDT 95.01 · 9 PDB
Residue 146: a UniProt-annotated variant site (in rp59; in a patient with congenital disorder of glycosylation)

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

Similar variants

DHDDS p.Asn146= Likely benign ★ same residue
DHDDS p.Asn146del 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

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-asn146lys (accessed [today's date]).

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