Is DPRX p.Pro174Leu (c.521C>T) pathogenic?

DPRX p.Pro174Leu (c.521C>T) is classified Uncertain significance in DPRX (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-10). AlphaMissense: likely benign (0.095); Ultra-rare (popmax 0.0187%, nfe).

How common is DPRX p.Pro174Leu (c.521C>T) in the general population?

DPRX p.Pro174Leu (c.521C>T) is ultra-rare (popmax 0.0187%, nfe) (gnomAD).

What do computational predictors say about DPRX p.Pro174Leu (c.521C>T)?

AlphaMissense predicts likely benign (score 0.095) — an in-silico prediction, not a clinical call.

DPRX p.Pro174Leu

c.521C>T · VCV4014681

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.095 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.095	likely benign
REVEL	0.131	moderately benign-leaning
SaProt	LLR -6.71	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 -0.05	GERP -2.6
Regional constraint	o/e 0.89	unconstrained · MANE · 4,878 bp · p 0.095 · regional, not allelic
Overall
CADD	5.868	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 0.0187% European (non-Finnish) · 220/1,179,466 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0158%

Overall 0.0141% 228/1,613,180 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0187%	5,361
Remaining individualsnot grpmax-eligible	0.00801%	12,487
African / African-American	0.004%	24,976

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.Pro174Leu
Coding: c.521C>T
MANE Select: NM_001012728
Type: single nucleotide variant
Location: chr19:53636933 (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-pro174leu (accessed [today's date]).

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