Is APC p.Asp1568= (c.4704T>C) pathogenic?

APC p.Asp1568= (c.4704T>C) is classified Benign/Likely benign in APC (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-26). Very rare (popmax 0.000169%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with APC p.Asp1568= (c.4704T>C)?

APC p.Asp1568= (c.4704T>C) is associated with hereditary neoplastic syndrome, familial adenomatous polyposis 1 (ClinVar).

How common is APC p.Asp1568= (c.4704T>C) in the general population?

APC p.Asp1568= (c.4704T>C) is very rare (popmax 0.000169%, nfe) (gnomAD).

APC p.Asp1568=

c.4704T>C · rs1554086117 · VCV482367

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

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 2.3	GERP 0.57, phastCons 1
Overall
CADD	8.377	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,179,976 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000205% 3/1,461,804 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,508
European (non-Finnish)grpmax	0.000169%	589,988

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp1568=
Coding: c.4704T>C
MANE Select: NM_000038
dbSNP: rs1554086117
Type: single nucleotide variant
Location: chr5:112840298 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1568: 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.Asp1568Asn Uncertain significance ★★ same residue
APC p.Asp1568Gly Uncertain significance ★★ same residue
APC p.Asp1568His Uncertain significance ★★ same residue
APC p.Asp1568_Asp1569insTer Pathogenic ★ same residue
APC p.Asp1568fs Pathogenic ★ 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

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-asp1568 (accessed [today's date]).

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