Is DPEP3 p.Asn98Asp (c.292A>G) pathogenic?

DPEP3 p.Asn98Asp (c.292A>G) is classified Uncertain significance in DPEP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-29). AlphaMissense: likely pathogenic (0.5655); Ultra-rare (popmax 0.0245%, eas).

How common is DPEP3 p.Asn98Asp (c.292A>G) in the general population?

DPEP3 p.Asn98Asp (c.292A>G) is ultra-rare (popmax 0.0245%, eas) (gnomAD).

What do computational predictors say about DPEP3 p.Asn98Asp (c.292A>G)?

AlphaMissense predicts likely pathogenic (score 0.5655) — an in-silico prediction, not a clinical call.

DPEP3 p.Asn98Asp

c.292A>G · rs370294992 · VCV2603146

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5655 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0245%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.5655	likely pathogenic
REVEL	0.394	indeterminate
SaProt	LLR -10.35	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.9	GERP 1.4, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 4,612 bp · p 0.0029 · regional, not allelic
Overall
CADD	27.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0245% East Asian · 11/44,874 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.000868% 14/1,613,810 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0245%	4,079
Remaining individualsnot grpmax-eligible	0.0048%	20,825

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: DPEP3
Protein: p.Asn98Asp
Coding: c.292A>G
MANE Select: NM_001370198
dbSNP: rs370294992
Type: single nucleotide variant
Location: chr16:67979761 (GRCh38)
Gene constraint: LOEUF 1.097 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.15 · 2 PDB
Residue 98: a β-strand

Full DPEP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPEP3 p.Asn98Ser Uncertain significance ★ ⚠ same residue
DPEP3 c.-44A>T Uncertain significance ★ same type
DPEP3 c.-47C>G Uncertain significance ★ same type
DPEP3 c.-5G>T Uncertain significance ★ same type
DPEP3 c.-62C>T Uncertain significance ★ same type
DPEP3 c.-6C>T Uncertain significance ★ same type
DPEP3 p.Ala11Thr Uncertain significance ★ ⚠ same type
DPEP3 p.Ala157Pro 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/dpep3-p-asn98asp (accessed [today's date]).

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