Is DTX1 p.Pro238Arg (c.713C>G) pathogenic?

DTX1 p.Pro238Arg (c.713C>G) is classified Uncertain significance in DTX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-28). AlphaMissense: likely benign (0.1049); Absent from gnomAD v4.1.

How common is DTX1 p.Pro238Arg (c.713C>G) in the general population?

DTX1 p.Pro238Arg (c.713C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DTX1 p.Pro238Arg (c.713C>G)?

AlphaMissense predicts likely benign (score 0.1049) — an in-silico prediction, not a clinical call.

DTX1 p.Pro238Arg

c.713C>G · VCV3273965

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1049 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,298,982)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1049	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	LLR -8.45	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 3.3	GERP 0.02, phastCons 0.37
Regional constraint	o/e 0.96	unconstrained · MANE · 17 kb · p 0.49 · regional, not allelic
Overall
CADD	17.11	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.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,298,982). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DTX1
Protein: p.Pro238Arg
Coding: c.713C>G
MANE Select: NM_004416
Type: single nucleotide variant
Location: chr12:113077877 (GRCh38)
Gene constraint: LOEUF 0.74 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.10 · 5 PDB
Residue 238: the 'disordered' region

Full DTX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DTX1 p.Gly445Asp Uncertain significance ★★ ⚠ same type
DTX1 p.Ser101= Benign ★★ same type
DTX1 p.Ala226Glu Uncertain significance ★ ⚠ same type
DTX1 p.Ala226Thr Uncertain significance ★ ⚠ same type
DTX1 p.Ala256Ser Uncertain significance ★ ⚠ same type
DTX1 p.Ala260Val Uncertain significance ★ ⚠ same type
DTX1 p.Ala267Pro Uncertain significance ★ ⚠ same type
DTX1 p.Ala275Val 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/dtx1-p-pro238arg (accessed [today's date]).

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