Is APC p.Asn804Ser (c.2411A>G) pathogenic?

APC p.Asn804Ser (c.2411A>G) is classified Conflicting classifications of pathogenicity in APC (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2025-09-29). AlphaMissense: likely benign (0.055); Very rare (popmax 0.00167%, amr); Associated with familial adenomatous polyposis 1.

What condition is associated with APC p.Asn804Ser (c.2411A>G)?

APC p.Asn804Ser (c.2411A>G) is associated with familial adenomatous polyposis 1, hereditary neoplastic syndrome, classic or attenuated familial adenomatous polyposis (ClinVar).

How common is APC p.Asn804Ser (c.2411A>G) in the general population?

APC p.Asn804Ser (c.2411A>G) is very rare (popmax 0.00167%, amr) (gnomAD).

How is Familial adenomatous polyposis inherited?

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

What do computational predictors say about APC p.Asn804Ser (c.2411A>G)?

AlphaMissense predicts likely benign (score 0.055) — an in-silico prediction, not a clinical call.

APC p.Asn804Ser

c.2411A>G · rs775727621 · VCV411401

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.055 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

familial adenomatous polyposis 1

Computational evidence

Protein change
AlphaMissense	0.055	likely benign
REVEL	0.184	benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.26	GERP -3.3, phastCons 0.027
Regional constraint	o/e 0.88	unconstrained · MANE · 256 bp · p 0.22 · regional, not allelic
Overall
CADD	3.752	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,010 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000434% 7/1,614,052 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,010
Remaining individualsnot grpmax-eligible	0.0016%	62,486
African / African-American	0.00133%	74,928
European (non-Finnish)	0.000339%	295,010

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.Asn804Ser
Coding: c.2411A>G
MANE Select: NM_000038
dbSNP: rs775727621
Type: single nucleotide variant
Location: chr5:112838005 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)

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.Asn804Asp Uncertain significance ★ ⚠ same residue
APC p.Asn804Lys Uncertain significance ★ ⚠ same residue
APC p.Asn804Thr Uncertain significance ★ ⚠ same residue
APC p.Asn804Tyr Uncertain significance ★ ⚠ 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
APC c.1312+5G>C 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-asn804ser (accessed [today's date]).

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