Is APP p.Asp247= (c.741C>T) pathogenic?

APP p.Asp247= (c.741C>T) is classified Benign/Likely benign in APP (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-08). Rare (popmax 0.419%, afr); Associated with Alzheimer disease.

What condition is associated with APP p.Asp247= (c.741C>T)?

APP p.Asp247= (c.741C>T) is associated with Alzheimer disease (ClinVar).

How common is APP p.Asp247= (c.741C>T) in the general population?

APP p.Asp247= (c.741C>T) is rare (popmax 0.419%, afr) (gnomAD).

APP p.Asp247=

c.741C>T · rs148832151 · VCV703233

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.419%, afr)

Conditions

Alzheimer disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.2	GERP -2.8
Overall
CADD	0.286	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.419% African / African-American · 314/74,990 alleles

Filtering AF 0.381% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.366%

Overall 0.0231% 372/1,613,742 alleles · rare exomes 221/1,461,592 · genomes 151/152,150 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.419%	239
Middle Eastern	0.066%	1,516
Remaining individualsnot grpmax-eligible	0.048%	2,083
Admixed American	0.0133%	7,494
South Asian	0.0044%	22,749
East Asian	0.00223%	44,872
European (non-Finnish)	0.000932%	107,261

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: APP
Protein: p.Asp247=
Coding: c.741C>T
MANE Select: NM_000484
dbSNP: rs148832151
Type: single nucleotide variant
Location: chr21:26021964 (GRCh38)
Gene constraint: LOEUF 0.41 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.11 · 263 PDB
Residue 247: the 'disordered' region

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

Disease context

Alzheimer disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

APP p.Ala713Thr Likely pathogenic ★★ ⚠ same condition
APP p.Asp694Asn Pathogenic ★★ ⚠ same condition
APP p.Glu693Gln Pathogenic ★★ ⚠ same condition
APP p.Ile716Phe Pathogenic ★★ ⚠ same condition
APP p.Thr714Ala Pathogenic ★★ ⚠ same condition
APP p.Val715Met Pathogenic/Likely pathogenic ★★ ⚠ same condition
APP p.Val717Ile Pathogenic ★★ ⚠ same condition
APP p.Val717Phe Pathogenic ★★ ⚠ same condition

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/app-p-asp247 (accessed [today's date]).

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