Is DPRX p.Thr85Ile (c.254C>T) pathogenic?

DPRX p.Thr85Ile (c.254C>T) is classified Uncertain significance in DPRX (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-17). AlphaMissense: likely benign (0.08); Very rare (popmax 8.47e-05%, nfe).

How common is DPRX p.Thr85Ile (c.254C>T) in the general population?

DPRX p.Thr85Ile (c.254C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about DPRX p.Thr85Ile (c.254C>T)?

AlphaMissense predicts likely benign (score 0.08) — an in-silico prediction, not a clinical call.

DPRX p.Thr85Ile

c.254C>T · rs2514029401 · VCV2308207

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.08 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.08	likely benign
REVEL	0.118	moderately benign-leaning
SaProt	LLR -6.66	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 0.26	GERP 1.4
Regional constraint	o/e 0.89	unconstrained · MANE · 4,878 bp · p 0.095 · regional, not allelic
Overall
CADD	1.239	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 8.47e-05% European (non-Finnish) · 1/1,179,982 alleles

Overall 6.84e-05% 1/1,461,830 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: DPRX
Protein: p.Thr85Ile
Coding: c.254C>T
MANE Select: NM_001012728
dbSNP: rs2514029401
Type: single nucleotide variant
Location: chr19:53636666 (GRCh38)
Gene constraint: LOEUF 1.777 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.08

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

Similar variants

DPRX p.Ala104Glu Uncertain significance ★ ⚠ same type
DPRX p.Ala173Thr Uncertain significance ★ ⚠ same type
DPRX p.Arg189Gln Uncertain significance ★ ⚠ same type
DPRX p.Arg189Gly Uncertain significance ★ ⚠ same type
DPRX p.Arg8Cys Uncertain significance ★ ⚠ same type
DPRX p.Asn103Asp Uncertain significance ★ ⚠ same type
DPRX p.Asn112Asp Uncertain significance ★ ⚠ same type
DPRX p.Gly146Ser 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/dprx-p-thr85ile (accessed [today's date]).

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