Is APC p.Asp1807= (c.5421C>T) pathogenic?

APC p.Asp1807= (c.5421C>T) is classified Benign/Likely benign in APC (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-07-21). Ultra-rare (popmax 0.0143%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with APC p.Asp1807= (c.5421C>T)?

APC p.Asp1807= (c.5421C>T) is associated with hereditary neoplastic syndrome, familial adenomatous polyposis 1 (ClinVar).

How common is APC p.Asp1807= (c.5421C>T) in the general population?

APC p.Asp1807= (c.5421C>T) is ultra-rare (popmax 0.0143%, sas) (gnomAD).

APC p.Asp1807=

c.5421C>T · rs753501921 · VCV487055

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0143%, sas)

Conditions

hereditary neoplastic syndrome

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 0.57	GERP 1, phastCons 1
Overall
CADD	4.376	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0143% South Asian · 13/90,968 alleles

Filtering AF 0.00845% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00662%

Overall 0.000932% 15/1,610,228 alleles · ultra-rare exomes 15/1,457,996 · genomes 0/152,232 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0143%	6,998
Remaining individualsnot grpmax-eligible	0.00321%	31,187

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: APC
Protein: p.Asp1807=
Coding: c.5421C>T
MANE Select: NM_000038
dbSNP: rs753501921
Type: single nucleotide variant
Location: chr5:112841015 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1807: the 'disordered' region

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial adenomatous polyposis 1

Similar variants

APC p.Asp1807Gly Uncertain significance ★★ same residue
APC p.Asp1807His Uncertain significance ★★ same residue
APC p.Asp1807Glu Uncertain significance ★ ⚠ same residue
APC c.1312+3A>C Likely pathogenic ★★★ same condition
APC c.1312+3A>G Pathogenic ★★★ same condition
APC c.1312+5G>A Likely pathogenic ★★★ same condition
APC c.1312+5G>C Likely pathogenic ★★★ same condition
APC c.1409-3T>G Likely 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/apc-p-asp1807 (accessed [today's date]).

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