Is DTHD1 p.Arg830Pro (c.2489G>C) pathogenic?

DTHD1 p.Arg830Pro (c.2489G>C) is classified Uncertain significance in DTHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-31). AlphaMissense: likely benign (0.257); Very rare (popmax 0.00244%, eas).

How common is DTHD1 p.Arg830Pro (c.2489G>C) in the general population?

DTHD1 p.Arg830Pro (c.2489G>C) is very rare (popmax 0.00244%, eas) (gnomAD).

What do computational predictors say about DTHD1 p.Arg830Pro (c.2489G>C)?

AlphaMissense predicts likely benign (score 0.257) — an in-silico prediction, not a clinical call.

DTHD1 p.Arg830Pro

c.2489G>C · VCV3618875

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.257 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00244%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.257	likely benign
REVEL	0.214	benign-leaning
SaProt	LLR -5.96	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 -0.11	GERP -3.8
Regional constraint	o/e 0.99	unconstrained · MANE · 62 kb · p 0.66 · regional, not allelic
Overall
CADD	14.8	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 R705P vs ClinVar R830P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00244% East Asian · 1/40,918 alleles

Overall 0.000143% 2/1,399,502 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00244%	40,918
Remaining individualsnot grpmax-eligible	0.00166%	60,180

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: DTHD1
Protein: p.Arg830Pro
Coding: c.2489G>C
MANE Select: NM_001170700
Type: single nucleotide variant
Location: chr4:36343592 (GRCh38)
Gene constraint: LOEUF 1.034 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.99

Full DTHD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DTHD1 p.Arg830Cys Uncertain significance ★★ ⚠ same residue
DTHD1 p.Arg830Gly Uncertain significance ★★ ⚠ same residue
DTHD1 p.Arg830His Uncertain significance ★ ⚠ same residue
DTHD1 c.1218+1G>A Uncertain significance ★★ same type
DTHD1 c.1219-2A>G Uncertain significance ★★ same type
DTHD1 p.Ala552Ser Uncertain significance ★★ ⚠ same type
DTHD1 p.Ala811Asp Uncertain significance ★★ ⚠ same type
DTHD1 p.Arg326Gln 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/dthd1-p-arg830pro (accessed [today's date]).

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