Is DNPEP p.Arg51Ser (c.151C>A) pathogenic?

DNPEP p.Arg51Ser (c.151C>A) is classified Uncertain significance in DNPEP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-18). AlphaMissense: ambiguous (0.5373); Very rare (popmax 0.00334%, amr).

How common is DNPEP p.Arg51Ser (c.151C>A) in the general population?

DNPEP p.Arg51Ser (c.151C>A) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about DNPEP p.Arg51Ser (c.151C>A)?

AlphaMissense predicts ambiguous (score 0.5373) — an in-silico prediction, not a clinical call.

DNPEP p.Arg51Ser

c.151C>A · rs1350556884 · VCV3084829

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5373 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Computational evidence

Protein change
AlphaMissense	0.5373	ambiguous
REVEL	0.33	indeterminate
SaProt	LLR -7.60	tolerated
Splicing
SpliceAI	Δ0.60	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 9.6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 13 kb · p 0.2 · regional, not allelic
Overall
CADD	34.0	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 0.00334% Admixed American · 2/59,952 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.00198% 3/151,800 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,976
African / African-American	0.00134%	74,780

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: DNPEP
Protein: p.Arg51Ser
Coding: c.151C>A
MANE Select: NM_012100
dbSNP: rs1350556884
Type: single nucleotide variant
Location: chr2:219386960 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.95 · 1 PDB
Residue 51: an α-helix

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

Similar variants

DNPEP p.Tyr308Cys Uncertain significance ★★ ⚠ same type
DNPEP p.Ile171Val Benign ★★ same type
DNPEP p.Ala204Thr Uncertain significance ★ ⚠ same type
DNPEP p.Ala221Thr Uncertain significance ★ ⚠ same type
DNPEP p.Ala263Ser Uncertain significance ★ ⚠ same type
DNPEP p.Ala27Val Uncertain significance ★ ⚠ same type
DNPEP p.Ala321Ser Uncertain significance ★ ⚠ same type
DNPEP p.Arg114His 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/dnpep-p-arg51ser (accessed [today's date]).

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