Is APC p.Asp2033Glu (c.6099C>G) pathogenic?

APC p.Asp2033Glu (c.6099C>G) is classified Conflicting classifications of pathogenicity in APC (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2025-12-21). AlphaMissense: likely pathogenic (0.9356); Very rare (popmax 0.00314%, nfe); Associated with classic or attenuated familial adenomatous polyposis.

What condition is associated with APC p.Asp2033Glu (c.6099C>G)?

APC p.Asp2033Glu (c.6099C>G) is associated with classic or attenuated familial adenomatous polyposis, hereditary neoplastic syndrome, familial adenomatous polyposis 1 (ClinVar).

How common is APC p.Asp2033Glu (c.6099C>G) in the general population?

APC p.Asp2033Glu (c.6099C>G) is very rare (popmax 0.00314%, nfe) (gnomAD).

What do computational predictors say about APC p.Asp2033Glu (c.6099C>G)?

AlphaMissense predicts likely pathogenic (score 0.9356) — an in-silico prediction, not a clinical call.

APC p.Asp2033Glu

c.6099C>G · rs370532497 · VCV181811

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely pathogenic

0.9356 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00314%, nfe)

Conditions

classic or attenuated familial adenomatous polyposis

Computational evidence

Protein change
AlphaMissense	0.9356	likely pathogenic
REVEL	0.425	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.29	GERP -5.5, phastCons 0.37
Regional constraint	o/e 1.08	unconstrained · MANE · 4,236 bp · p 0.00065 · regional, not allelic
Overall
CADD	19.5	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 0.00314% European (non-Finnish) · 37/1,179,774 alleles

Filtering AF 0.00231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00202%

Overall 0.00235% 38/1,613,756 alleles · very rare exomes 34/1,461,590 · genomes 4/152,166 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00314%	31,886
Remaining individualsnot grpmax-eligible	0.0016%	62,478

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.Asp2033Glu
Coding: c.6099C>G
MANE Select: NM_000038
dbSNP: rs370532497
Type: single nucleotide variant
Location: chr5:112841693 (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 familial adenomatous polyposis 1

Similar variants

APC p.Asp2033= Benign/Likely benign ★★ same residue
APC p.Asp2033Asn Uncertain significance ★ same residue
APC p.Asp2033_Ser2034insTer Pathogenic ★★ 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-asp2033glu (accessed [today's date]).

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