Is DPRX p.Pro57Ser (c.169C>T) pathogenic?

DPRX p.Pro57Ser (c.169C>T) is classified Uncertain significance in DPRX (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-30). AlphaMissense: likely pathogenic (0.7458); Ultra-rare (popmax 0.0131%, nfe).

How common is DPRX p.Pro57Ser (c.169C>T) in the general population?

DPRX p.Pro57Ser (c.169C>T) is ultra-rare (popmax 0.0131%, nfe) (gnomAD).

What do computational predictors say about DPRX p.Pro57Ser (c.169C>T)?

AlphaMissense predicts likely pathogenic (score 0.7458) — an in-silico prediction, not a clinical call.

DPRX p.Pro57Ser

c.169C>T · VCV3505038

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7458 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0131%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7458	likely pathogenic
REVEL	0.374	indeterminate
SaProt	LLR -9.51	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -2.9, phastCons 0.007
Regional constraint	o/e 0.89	unconstrained · MANE · 4,878 bp · p 0.095 · regional, not allelic
Overall
CADD	16.07	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0131% European (non-Finnish) · 155/1,179,816 alleles

Filtering AF 0.0114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0107%

Overall 0.00973% 157/1,613,376 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0131%	7,612
Remaining individualsnot grpmax-eligible	0.0032%	31,231

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.Pro57Ser
Coding: c.169C>T
MANE Select: NM_001012728
Type: single nucleotide variant
Location: chr19:53634671 (GRCh38)
Gene constraint: LOEUF 1.777 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.08
Residue 57: a DNA-binding region

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-pro57ser (accessed [today's date]).

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