Is DDOST p.Thr5Ser (c.14C>G) pathogenic?

DDOST p.Thr5Ser (c.14C>G) is classified Uncertain significance in DDOST (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-30). AlphaMissense: likely benign (0.0711); Very rare (popmax 0.000509%, nfe).

How common is DDOST p.Thr5Ser (c.14C>G) in the general population?

DDOST p.Thr5Ser (c.14C>G) is very rare (popmax 0.000509%, nfe) (gnomAD).

What do computational predictors say about DDOST p.Thr5Ser (c.14C>G)?

AlphaMissense predicts likely benign (score 0.0711) — an in-silico prediction, not a clinical call.

DDOST p.Thr5Ser

c.14C>G · rs770989718 · VCV2329995

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0711 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000509%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0711	likely benign
REVEL	0.014	strongly benign-leaning
SaProt	LLR -5.32	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 0.44	GERP -3.7
Regional constraint	o/e 0.92	unconstrained · MANE · 8,968 bp · p 0.046 · regional, not allelic
Overall
CADD	0.12	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM T22S vs ClinVar T5S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000509% European (non-Finnish) · 6/1,179,934 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000411% 6/1,460,962 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: DDOST
Protein: p.Thr5Ser
Coding: c.14C>G
MANE Select: NM_005216
dbSNP: rs770989718
Type: single nucleotide variant
Location: chr1:20661337 (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.Arg5Gln Uncertain significance ★ ⚠ same residue
DDOST p.Arg5Trp Uncertain significance ★ ⚠ same residue
DDOST p.Thr5Ile Uncertain significance ★ ⚠ 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

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-thr5ser (accessed [today's date]).

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