Is DNPEP p.Val24Met (c.70G>A) pathogenic?

DNPEP p.Val24Met (c.70G>A) is classified Uncertain significance in DNPEP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-13). AlphaMissense: likely benign (0.2322); Absent from gnomAD v4.1.

How common is DNPEP p.Val24Met (c.70G>A) in the general population?

DNPEP p.Val24Met (c.70G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DNPEP p.Val24Met (c.70G>A)?

AlphaMissense predicts likely benign (score 0.2322) — an in-silico prediction, not a clinical call.

DNPEP p.Val24Met

c.70G>A · VCV4661569

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2322 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,569,742)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2322	likely benign
REVEL	0.086	moderately benign-leaning
SaProt	LLR -7.21	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 2.5	GERP 0.33, phastCons 0.99
Regional constraint	o/e 0.95	unconstrained · MANE · 13 kb · p 0.2 · regional, not allelic
Overall
CADD	17.75	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

No allele count reported in gnomAD v4.1 (AN 1,569,742). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DNPEP
Protein: p.Val24Met
Coding: c.70G>A
MANE Select: NM_012100
Type: single nucleotide variant
Location: chr2:219387130 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.95 · 1 PDB
Residue 24: 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-val24met (accessed [today's date]).

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