Is DNPEP p.Glu161Asp (c.483G>C) pathogenic?

DNPEP p.Glu161Asp (c.483G>C) is classified Uncertain significance in DNPEP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-10). AlphaMissense: likely benign (0.236); Ultra-rare (popmax 0.0894%, afr).

How common is DNPEP p.Glu161Asp (c.483G>C) in the general population?

DNPEP p.Glu161Asp (c.483G>C) is ultra-rare (popmax 0.0894%, afr) (gnomAD).

What do computational predictors say about DNPEP p.Glu161Asp (c.483G>C)?

AlphaMissense predicts likely benign (score 0.236) — an in-silico prediction, not a clinical call.

DNPEP p.Glu161Asp

c.483G>C · rs367736817 · VCV2396770

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.236 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0894%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.236	likely benign
REVEL	0.069	moderately benign-leaning
SaProt	LLR -9.69	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 -0.16	GERP 0.37, phastCons 0.4
Regional constraint	o/e 0.95	unconstrained · MANE · 13 kb · p 0.2 · regional, not allelic
Overall
CADD	17.12	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 0.0894% African / African-American · 67/74,920 alleles

Filtering AF 0.0722% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.066%

Overall 0.00415% 67/1,614,044 alleles · ultra-rare

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.Glu161Asp
Coding: c.483G>C
MANE Select: NM_012100
dbSNP: rs367736817
Type: single nucleotide variant
Location: chr2:219386075 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.95 · 1 PDB
Residue 161: a β-strand

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-glu161asp (accessed [today's date]).

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