Is DPRX p.Pro135Ser (c.403C>T) pathogenic?

DPRX p.Pro135Ser (c.403C>T) is classified Uncertain significance in DPRX (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). AlphaMissense: likely benign (0.1357); Ultra-rare (popmax 0.0156%, nfe).

How common is DPRX p.Pro135Ser (c.403C>T) in the general population?

DPRX p.Pro135Ser (c.403C>T) is ultra-rare (popmax 0.0156%, nfe) (gnomAD).

What do computational predictors say about DPRX p.Pro135Ser (c.403C>T)?

AlphaMissense predicts likely benign (score 0.1357) — an in-silico prediction, not a clinical call.

DPRX p.Pro135Ser

c.403C>T · rs376708716 · VCV2590782

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1357 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1357	likely benign
REVEL	0.238	benign-leaning
SaProt	LLR -7.86	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 -0.19	GERP -0.55
Regional constraint	o/e 0.89	unconstrained · MANE · 4,878 bp · p 0.095 · regional, not allelic
Overall
CADD	2.162	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 0.0156% European (non-Finnish) · 184/1,180,028 alleles

Filtering AF 0.0138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.013%

Overall 0.0123% 199/1,613,962 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0156%	6,413
Finnishnot grpmax-eligible	0.00781%	12,806
Remaining individualsnot grpmax-eligible	0.0064%	15,622
African / African-American	0.00534%	18,718
Admixed American	0.00334%	29,978

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.Pro135Ser
Coding: c.403C>T
MANE Select: NM_001012728
dbSNP: rs376708716
Type: single nucleotide variant
Location: chr19:53636815 (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-pro135ser (accessed [today's date]).

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