Is DDOST p.Arg265Ser (c.795G>C) pathogenic?

DDOST p.Arg265Ser (c.795G>C) is classified Uncertain significance in DDOST (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-11). AlphaMissense: ambiguous (0.4293); Absent from gnomAD v4.1.

How common is DDOST p.Arg265Ser (c.795G>C) in the general population?

DDOST p.Arg265Ser (c.795G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DDOST p.Arg265Ser (c.795G>C)?

AlphaMissense predicts ambiguous (score 0.4293) — an in-silico prediction, not a clinical call.

DDOST p.Arg265Ser

c.795G>C · VCV4010058

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4293 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4293	ambiguous
REVEL	0.389	indeterminate
SaProt	LLR -7.97	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP 1.2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 8,968 bp · p 0.046 · regional, not allelic
Overall
CADD	22.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R282S vs ClinVar R265S) — verify the residue.

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: DDOST
Protein: p.Arg265Ser
Coding: c.795G>C
MANE Select: NM_005216
Type: single nucleotide variant
Location: chr1:20653774 (GRCh38)
Gene constraint: LOEUF 0.747 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 89.27 · 6 PDB

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

Similar variants

DDOST p.Arg265= Conflicting classifications of pathogenicity ★ same residue
DDOST p.Gln215His Pathogenic/Likely pathogenic ★★ ⚠ same type
DDOST c.-18T>G Uncertain significance ★★ ⚠ same type
DDOST p.Ala11Val Uncertain significance ★★ ⚠ same type
DDOST p.Ala219Val Uncertain significance ★★ ⚠ same type
DDOST p.Ala232Ser Uncertain significance ★★ ⚠ same type
DDOST p.Ala415Thr Uncertain significance ★★ ⚠ same type
DDOST p.Arg237His Uncertain significance ★★ ⚠ 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/ddost-p-arg265ser (accessed [today's date]).

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