Is DTL p.Pro698Arg (c.2093C>G) pathogenic?

DTL p.Pro698Arg (c.2093C>G) is classified Uncertain significance in DTL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-06). AlphaMissense: likely benign (0.1356); Ultra-rare (popmax 0.0223%, amr).

How common is DTL p.Pro698Arg (c.2093C>G) in the general population?

DTL p.Pro698Arg (c.2093C>G) is ultra-rare (popmax 0.0223%, amr) (gnomAD).

What do computational predictors say about DTL p.Pro698Arg (c.2093C>G)?

AlphaMissense predicts likely benign (score 0.1356) — an in-silico prediction, not a clinical call.

DTL p.Pro698Arg

c.2093C>G · rs557642530 · VCV3086071

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1356 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0223%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1356	likely benign
REVEL	0.187	benign-leaning
SaProt	LLR -7.17	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 1.2	GERP -2.3, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 67 kb · p 7.1e-06 · regional, not allelic
Overall
CADD	15.37	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

Grpmax group 0.0223% Admixed American · 13/58,338 alleles

Filtering AF 0.0131% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0104%

Overall 0.00132% 21/1,596,946 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0223%	4,488
Middle Eastern	0.0168%	5,968
Remaining individualsnot grpmax-eligible	0.00485%	20,619
European (non-Finnish)	0.000341%	292,967

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: DTL
Protein: p.Pro698Arg
Coding: c.2093C>G
MANE Select: NM_016448
dbSNP: rs557642530
Type: single nucleotide variant
Location: chr1:212101083 (GRCh38)
Gene constraint: LOEUF 0.635 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.29 · 5 PDB
Residue 698: the 'disordered' region

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

Similar variants

DTL p.Pro698Leu Uncertain significance ★ ⚠ same residue
DTL p.Arg715= Benign ★★ same type
DTL p.Ala210Val Uncertain significance ★ ⚠ same type
DTL p.Ala474Gly Uncertain significance ★ ⚠ same type
DTL p.Arg389Ser Uncertain significance ★ ⚠ same type
DTL p.Arg482Lys Uncertain significance ★ ⚠ same type
DTL p.Arg502Gly Uncertain significance ★ ⚠ same type
DTL p.Arg670Gln 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/dtl-p-pro698arg (accessed [today's date]).

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