Is DHDDS p.Ser303fs (c.908_941del) pathogenic?

DHDDS p.Ser303fs (c.908941del) is classified Uncertain significance in DHDDS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-10). Very rare (popmax 8.47e-05%, nfe).

How common is DHDDS p.Ser303fs (c.908_941del) in the general population?

DHDDS p.Ser303fs (c.908_941del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

DHDDS p.Ser303fs

c.908_941del · rs2524816772 · VCV2577160

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	escapes	premature termination codon in the last exon (9 of 9) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.3	GERP 1.7, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,032 alleles

Overall 6.84e-05% 1/1,461,706 alleles · very rare

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: DHDDS
Protein: p.Ser303fs
Coding: c.908_941del
MANE Select: NM_205861
dbSNP: rs2524816772
Type: Deletion
Location: chr1:26469035 (GRCh38)
Gene constraint: LOEUF 0.536 · pLI 0.91 (gnomAD)
Structure: AlphaFold pLDDT 95.01 · 9 PDB
Residue 303: a UniProt-annotated variant site (in rp59; in a patient with congenital disorder of glycosylation); an α-helix

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

Similar variants

DHDDS p.Ser303Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
DHDDS p.Ser303Pro Uncertain significance ★ ⚠ same residue
DHDDS p.Ser303= Likely benign ★ same residue
DHDDS p.His222fs Likely pathogenic ★★ same type
DHDDS p.Ser88fs Pathogenic/Likely pathogenic ★★ same type
DHDDS c.650_657+54del Likely pathogenic ★ same type
DHDDS p.Asp34fs Pathogenic ★ same type
DHDDS p.Phe215fs 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-ser303fs (accessed [today's date]).

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