Is DDOST p.Arg342His (c.1025G>A) pathogenic?

DDOST p.Arg342His (c.1025G>A) is classified Uncertain significance in DDOST (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-29). AlphaMissense: likely pathogenic (0.9822); Very rare (popmax 0.00659%, sas).

How common is DDOST p.Arg342His (c.1025G>A) in the general population?

DDOST p.Arg342His (c.1025G>A) is very rare (popmax 0.00659%, sas) (gnomAD).

What do computational predictors say about DDOST p.Arg342His (c.1025G>A)?

AlphaMissense predicts likely pathogenic (score 0.9822) — an in-silico prediction, not a clinical call.

DDOST p.Arg342His

c.1025G>A · rs776936181 · VCV2258070

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9822 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9822	likely pathogenic
REVEL	0.862	moderately pathogenic-leaning
SaProt	LLR -8.74	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 8,968 bp · p 0.046 · regional, not allelic
Overall
CADD	33.0	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 R359H vs ClinVar R342H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00659% South Asian · 6/91,080 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.000821% 12/1,461,878 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00659%	15,180
African / African-American	0.00133%	75,052
European (non-Finnish)	0.000424%	236,007

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.Arg342His
Coding: c.1025G>A
MANE Select: NM_005216
dbSNP: rs776936181
Type: single nucleotide variant
Location: chr1:20652889 (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.Arg342Cys 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
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-arg342his (accessed [today's date]).

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