Is DAPP1 p.Asp104Asn (c.310G>A) pathogenic?

DAPP1 p.Asp104Asn (c.310G>A) is classified Uncertain significance in DAPP1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-04-23). AlphaMissense: likely benign (0.1504); Very rare (popmax 8.48e-05%, nfe); Associated with DAPP1-related condition.

What condition is associated with DAPP1 p.Asp104Asn (c.310G>A)?

DAPP1 p.Asp104Asn (c.310G>A) is associated with DAPP1-related condition (ClinVar).

How common is DAPP1 p.Asp104Asn (c.310G>A) in the general population?

DAPP1 p.Asp104Asn (c.310G>A) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about DAPP1 p.Asp104Asn (c.310G>A)?

AlphaMissense predicts likely benign (score 0.1504) — an in-silico prediction, not a clinical call.

DAPP1 p.Asp104Asn

c.310G>A · VCV3358370

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1504 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

DAPP1-related condition

Computational evidence

Protein change
AlphaMissense	0.1504	likely benign
REVEL	0.519	indeterminate
SaProt	LLR -8.72	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 6.7, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 51 kb · p 3.8e-08 · regional, not allelic
Overall
CADD	25.4	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 8.48e-05% European (non-Finnish) · 1/1,179,008 alleles

Overall 6.85e-05% 1/1,458,902 alleles · very 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: DAPP1
Protein: p.Asp104Asn
Coding: c.310G>A
MANE Select: NM_014395
Type: single nucleotide variant
Location: chr4:99840374 (GRCh38)
Gene constraint: LOEUF 0.905 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.43 · 2 PDB
Residue 104: the sh2 domain

Full DAPP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DAPP1-related condition

Similar variants

DAPP1 p.Ala215Thr Uncertain significance ★ ⚠ same type
DAPP1 p.Arg143Gln Uncertain significance ★ ⚠ same type
DAPP1 p.Arg255His Uncertain significance ★ ⚠ same type
DAPP1 p.Arg262Ile Uncertain significance ★ ⚠ same type
DAPP1 p.Arg275Trp Uncertain significance ★ ⚠ same type
DAPP1 p.Asp15Asn Uncertain significance ★ ⚠ same type
DAPP1 p.Asp15Glu Uncertain significance ★ ⚠ same type
DAPP1 p.Asp219Asn 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/dapp1-p-asp104asn (accessed [today's date]).

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