Is APC p.Asp539= (c.1617C>T) pathogenic?

APC p.Asp539= (c.1617C>T) is classified Benign/Likely benign in APC (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-11-12). Very rare (popmax 0.00879%, sas); Associated with familial adenomatous polyposis 1.

What condition is associated with APC p.Asp539= (c.1617C>T)?

APC p.Asp539= (c.1617C>T) is associated with familial adenomatous polyposis 1, hereditary neoplastic syndrome, classic or attenuated familial adenomatous polyposis (ClinVar).

How common is APC p.Asp539= (c.1617C>T) in the general population?

APC p.Asp539= (c.1617C>T) is very rare (popmax 0.00879%, sas) (gnomAD).

How is Familial adenomatous polyposis inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

APC p.Asp539=

c.1617C>T · rs1554081912 · VCV490216

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00879%, sas)

Conditions

familial adenomatous polyposis 1

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 0.84	GERP 0.08, phastCons 1
Overall
CADD	10.88	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00879% South Asian · 8/90,994 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00312%

Overall 0.000617% 9/1,459,842 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00879%	11,374
African / African-American	0.00133%	74,974

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.Asp539=
Coding: c.1617C>T
MANE Select: NM_000038
dbSNP: rs1554081912
Type: single nucleotide variant
Location: chr5:112827997 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 539: an α-helix

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

Disease context

familial adenomatous polyposis 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome classic or attenuated familial adenomatous polyposis

For Familial adenomatous polyposis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Adult
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

APC p.Asp539Gly Uncertain significance ★★ ⚠ same residue
APC p.Asp539Ala Uncertain significance ★ ⚠ same residue
APC p.Asp539Glu Uncertain significance ★ ⚠ same residue
APC p.Asp539Tyr Uncertain significance ★ same residue
APC p.Asp539Val Uncertain significance ★ ⚠ same residue
APC p.Asp539fs Pathogenic ★ same residue
APC c.1312+3A>C Likely pathogenic ★★★ same condition
APC c.1312+3A>G 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-asp539 (accessed [today's date]).

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