Is DHDDS p.Ser213Asn (c.638G>A) pathogenic?

DHDDS p.Ser213Asn (c.638G>A) is classified Likely pathogenic in DHDDS (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-21). AlphaMissense: likely pathogenic (0.9987); Absent from gnomAD v4.1; Associated with DHDDS-related disorder.

What condition is associated with DHDDS p.Ser213Asn (c.638G>A)?

DHDDS p.Ser213Asn (c.638G>A) is associated with DHDDS-related disorder (ClinVar).

How common is DHDDS p.Ser213Asn (c.638G>A) in the general population?

DHDDS p.Ser213Asn (c.638G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DHDDS p.Ser213Asn (c.638G>A)?

AlphaMissense predicts likely pathogenic (score 0.9987) — an in-silico prediction, not a clinical call.

DHDDS p.Ser213Asn

c.638G>A · rs2524687222 · VCV2637052

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9987 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DHDDS-related disorder

Computational evidence

Protein change
AlphaMissense	0.9987	likely pathogenic ✓ concordant with ClinVar · top 3% in DHDDS
REVEL	0.706	pathogenic-leaning
SaProt	LLR -13.98	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 26 kb · p 0.063 · regional, not allelic
Overall
CADD	32.0	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.Ser213Asn
Coding: c.638G>A
MANE Select: NM_205861
dbSNP: rs2524687222
Type: single nucleotide variant
Location: chr1:26457886 (GRCh38)
Gene constraint: LOEUF 0.536 · pLI 0.91 (gnomAD)
Structure: AlphaFold pLDDT 95.01 · 9 PDB
Residue 213: a binding site; 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

Disease context

DHDDS-related disorder

Similar variants

DHDDS p.Lys42Glu Pathogenic ★★ ⚠ same condition
DHDDS p.Asp123Asn Uncertain significance ★★ ⚠ same condition
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-ser213asn (accessed [today's date]).

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