Is APC p.Lys150= (c.450A>G) pathogenic?

APC p.Lys150= (c.450A>G) is classified Conflicting classifications of pathogenicity in APC (ClinVar, Conflicting submitters, 20 submitters; last evaluated 2026-06-01). Ultra-rare (popmax 0.0296%, nfe); Associated with classic or attenuated familial adenomatous polyposis.

What condition is associated with APC p.Lys150= (c.450A>G)?

APC p.Lys150= (c.450A>G) is associated with classic or attenuated familial adenomatous polyposis, colon carcinoma, hereditary neoplastic syndrome (ClinVar).

How common is APC p.Lys150= (c.450A>G) in the general population?

APC p.Lys150= (c.450A>G) is ultra-rare (popmax 0.0296%, nfe) (gnomAD).

APC p.Lys150=

c.450A>G · rs116020626 · VCV181782

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 20 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0296%, nfe)

Conditions

classic or attenuated familial adenomatous polyposis

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 7.9	phastCons 1
Overall
CADD	10.67	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0296% European (non-Finnish) · 349/1,177,422 alleles

Filtering AF 0.027% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.026%

Overall 0.0231% 371/1,608,332 alleles · ultra-rare exomes 351/1,456,126 · genomes 20/152,206 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0296%	3,374
Remaining individualsnot grpmax-eligible	0.0177%	5,663
South Asian	0.0056%	17,859
Admixed American	0.00503%	19,873
Finnishnot grpmax-eligible	0.00313%	31,963
African / African-American	0.00134%	74,802

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.Lys150=
Coding: c.450A>G
MANE Select: NM_000038
dbSNP: rs116020626
Type: single nucleotide variant
Location: chr5:112775656 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 150: an α-helix

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

Disease context

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

Also linked: colon carcinoma hereditary neoplastic syndrome familial adenomatous polyposis 1

Similar variants

APC p.Lys150Ter Pathogenic ★★ same residue
APC p.Lys150Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
APC p.Lys150Gln Uncertain significance ★ ⚠ same residue
APC p.Lys150fs Pathogenic/Likely pathogenic ★★ same residue
APC p.Lys150del Uncertain significance ★ same residue
APC p.Lys150Ile Uncertain significance ★ ⚠ 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-lys150 (accessed [today's date]).

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