Is APC p.Ser367Cys (c.1100C>G) pathogenic?

APC p.Ser367Cys (c.1100C>G) is classified Uncertain significance in APC (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-04-25). AlphaMissense: likely benign (0.2998); Very rare (popmax 8.47e-05%, nfe); Associated with classic or attenuated familial adenomatous polyposis.

How common is APC p.Ser367Cys (c.1100C>G) in the general population?

APC p.Ser367Cys (c.1100C>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about APC p.Ser367Cys (c.1100C>G)?

AlphaMissense predicts likely benign (score 0.2998) — an in-silico prediction, not a clinical call.

APC p.Ser367Cys

Q: What condition is associated with APC p.Ser367Cys (c.1100C>G)?

APC p.Ser367Cys (c.1100C>G) is associated with classic or attenuated familial adenomatous polyposis, hereditary neoplastic syndrome (ClinVar).

c.1100C>G · rs1554080012 · VCV495350

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2998 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Conditions

classic or attenuated familial adenomatous polyposis

Computational evidence

Protein change
AlphaMissense	0.2998	likely benign
REVEL	0.682	pathogenic-leaning
⇒ REVEL calls this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.9, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 8,173 bp · p 0.36 · regional, not allelic
Overall
CADD	28.4	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 8.47e-05% European (non-Finnish) · 1/1,179,992 alleles

Overall 6.84e-05% 1/1,461,770 alleles · very rare

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.Ser367Cys
Coding: c.1100C>G
MANE Select: NM_000038
dbSNP: rs1554080012
Type: single nucleotide variant
Location: chr5:112819132 (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

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

Also linked: hereditary neoplastic syndrome

Similar variants

APC p.Ser367Thr Uncertain significance ★★ same residue
APC p.Ser367= Likely benign ★★ same residue
APC p.Ser367Tyr 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
APC c.1409-3T>G 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-ser367cys (accessed [today's date]).

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