Is APC p.Lys150Arg (c.449A>G) pathogenic?

APC p.Lys150Arg (c.449A>G) is classified Conflicting classifications of pathogenicity in APC (ClinVar, Conflicting submitters, 17 submitters; last evaluated 2026-04-06). AlphaMissense: likely benign (0.0913); Very rare (popmax 0.0079%, nfe); Associated with classic or attenuated familial adenomatous polyposis.

What condition is associated with APC p.Lys150Arg (c.449A>G)?

APC p.Lys150Arg (c.449A>G) is associated with classic or attenuated familial adenomatous polyposis, colorectal adenoma, hereditary neoplastic syndrome (ClinVar).

How common is APC p.Lys150Arg (c.449A>G) in the general population?

APC p.Lys150Arg (c.449A>G) is very rare (popmax 0.0079%, nfe) (gnomAD).

What do computational predictors say about APC p.Lys150Arg (c.449A>G)?

AlphaMissense predicts likely benign (score 0.0913) — an in-silico prediction, not a clinical call.

APC p.Lys150Arg

c.449A>G · rs371085910 · VCV141928

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 17 submitters

AlphaMissense

likely benign

0.0913 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0079%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

classic or attenuated familial adenomatous polyposis

Computational evidence

Protein change
AlphaMissense	0.0913	likely benign
REVEL	0.871	moderately pathogenic-leaning
SaProt	—	not scored · why
⇒ REVEL calls this damaging; AlphaMissense does not; SaProt makes no call.
Splicing
SpliceAI	Δ0.24	acceptor loss, 26 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 11	phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 61 kb · p 0.82 · regional, not allelic
Overall
CADD	22.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0079% European (non-Finnish) · 93/1,177,594 alleles

Filtering AF 0.00657% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00609%

Overall 0.00616% 99/1,608,404 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0079%	12,662
Remaining individualsnot grpmax-eligible	0.00482%	20,759
South Asian	0.00224%	44,652
African / African-American	0.00134%	74,682

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.Lys150Arg
Coding: c.449A>G
MANE Select: NM_000038
dbSNP: rs371085910
Type: single nucleotide variant
Location: chr5:112775655 (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: colorectal adenoma hereditary neoplastic syndrome familial adenomatous polyposis 1

Similar variants

APC p.Lys150Ter Pathogenic ★★ same residue
APC p.Lys150= 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-lys150arg (accessed [today's date]).

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