Is DPRX p.Ser44Arg (c.132C>G) pathogenic?

DPRX p.Ser44Arg (c.132C>G) is classified Uncertain significance in DPRX (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-24). AlphaMissense: ambiguous (0.4692); Very rare (popmax 0.00432%, nfe).

How common is DPRX p.Ser44Arg (c.132C>G) in the general population?

DPRX p.Ser44Arg (c.132C>G) is very rare (popmax 0.00432%, nfe) (gnomAD).

What do computational predictors say about DPRX p.Ser44Arg (c.132C>G)?

AlphaMissense predicts ambiguous (score 0.4692) — an in-silico prediction, not a clinical call.

DPRX p.Ser44Arg

c.132C>G · VCV4662026

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4692 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00432%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4692	ambiguous
REVEL	0.281	benign-leaning
SaProt	LLR -6.96	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1	GERP -3
Regional constraint	o/e 0.89	unconstrained · MANE · 4,878 bp · p 0.095 · regional, not allelic
Overall
CADD	12.64	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 0.00432% European (non-Finnish) · 51/1,179,968 alleles

Filtering AF 0.00334% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00302%

Overall 0.00328% 53/1,613,940 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00432%	23,137
Remaining individualsnot grpmax-eligible	0.0016%	62,476
African / African-American	0.00133%	74,926

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.Ser44Arg
Coding: c.132C>G
MANE Select: NM_001012728
Type: single nucleotide variant
Location: chr19:53634634 (GRCh38)
Gene constraint: LOEUF 1.777 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.08
Residue 44: 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-ser44arg (accessed [today's date]).

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