Is DAPP1 p.Arg143Gln (c.428G>A) pathogenic?

DAPP1 p.Arg143Gln (c.428G>A) is classified Uncertain significance in DAPP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-25). AlphaMissense: likely benign (0.1821); Ultra-rare (popmax 0.0357%, eas).

How common is DAPP1 p.Arg143Gln (c.428G>A) in the general population?

DAPP1 p.Arg143Gln (c.428G>A) is ultra-rare (popmax 0.0357%, eas) (gnomAD).

What do computational predictors say about DAPP1 p.Arg143Gln (c.428G>A)?

AlphaMissense predicts likely benign (score 0.1821) — an in-silico prediction, not a clinical call.

DAPP1 p.Arg143Gln

c.428G>A · VCV4237611

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1821 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0357%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1821	likely benign
REVEL	0.269	benign-leaning
SaProt	LLR -2.06	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 12	GERP 7, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 51 kb · p 3.8e-08 · regional, not allelic
Overall
CADD	26.9	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 0.0357% East Asian · 16/44,852 alleles

Filtering AF 0.0223% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0182%

Overall 0.00205% 33/1,613,282 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0357%	2,803
African / African-American	0.00667%	15,001
Remaining individualsnot grpmax-eligible	0.0048%	20,825
Admixed American	0.00167%	59,924
European (non-Finnish)	0.000678%	147,451

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.Arg143Gln
Coding: c.428G>A
MANE Select: NM_014395
Type: single nucleotide variant
Location: chr4:99853287 (GRCh38)
Gene constraint: LOEUF 0.905 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.43 · 2 PDB

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

Similar variants

DAPP1 p.Ala215Thr 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
DAPP1 p.Gln260His 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-arg143gln (accessed [today's date]).

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