Is DHDDS p.Lys147= (c.441G>A) pathogenic?

DHDDS p.Lys147= (c.441G>A) is classified Likely benign in DHDDS (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-20). Very rare (popmax 0.000254%, nfe).

How common is DHDDS p.Lys147= (c.441G>A) in the general population?

DHDDS p.Lys147= (c.441G>A) is very rare (popmax 0.000254%, nfe) (gnomAD).

DHDDS p.Lys147=

c.441G>A · VCV4963279

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.214	benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.45 · evaluated, not missing
Pangolin	Δ0.29	loss · gain 0.07 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 5.8	GERP 0.88, phastCons 1
Overall
CADD	17.06	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,106 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.00322% 52/1,612,980 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0687%	1,455
Remaining individualsnot grpmax-eligible	0.00801%	12,489
European (non-Finnish)grpmax	0.000254%	393,035

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Lys147=
Coding: c.441G>A
MANE Select: NM_205861
Type: single nucleotide variant
Location: chr1:26447559 (GRCh38)
Gene constraint: LOEUF 0.536 · pLI 0.91 (gnomAD)
Structure: AlphaFold pLDDT 95.01 · 9 PDB
Residue 147: a UniProt-annotated variant site (in rp59; in a patient with congenital disorder of glycosylation); a β-strand

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

Similar variants

DHDDS p.Lys147Arg 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-lys147 (accessed [today's date]).

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