Is APC p.Asp209= (c.627T>C) pathogenic?

APC p.Asp209= (c.627T>C) is classified Benign/Likely benign in APC (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-11-21). Ultra-rare (popmax 0.0165%, mid); Associated with hereditary neoplastic syndrome.

What condition is associated with APC p.Asp209= (c.627T>C)?

APC p.Asp209= (c.627T>C) is associated with hereditary neoplastic syndrome, familial adenomatous polyposis 1, classic or attenuated familial adenomatous polyposis (ClinVar).

How common is APC p.Asp209= (c.627T>C) in the general population?

APC p.Asp209= (c.627T>C) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

APC p.Asp209=

c.627T>C · rs1373069696 · VCV918441

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

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 -0.27	phastCons 0.45
Overall
CADD	6.833	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,058 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000343% 5/1,459,060 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,058
Remaining individualsnot grpmax-eligible	0.0016%	62,400
European (non-Finnish)	0.000255%	392,636

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.Asp209=
Coding: c.627T>C
MANE Select: NM_000038
dbSNP: rs1373069696
Type: single nucleotide variant
Location: chr5:112780885 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 209: an α-helix

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 classic or attenuated familial adenomatous polyposis

Similar variants

APC p.Asp209Asn Uncertain significance ★★ same residue
APC p.Asp209Gly Uncertain significance ★★ same residue
APC p.Asp209Val Uncertain significance ★★ ⚠ same residue
APC p.Asp209Glu Uncertain significance ★ same residue
APC p.Asp209Tyr Uncertain significance ★ same residue
APC p.Asp209fs 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-asp209 (accessed [today's date]).

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