Is APC p.Asp29Glu (c.87T>G) pathogenic?

APC p.Asp29Glu (c.87T>G) is classified Uncertain significance in APC (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-06). AlphaMissense: likely pathogenic (0.6096); Ultra-rare (popmax 0.0165%, mid); Associated with familial adenomatous polyposis 1.

What condition is associated with APC p.Asp29Glu (c.87T>G)?

APC p.Asp29Glu (c.87T>G) is associated with familial adenomatous polyposis 1 (ClinVar).

How common is APC p.Asp29Glu (c.87T>G) in the general population?

APC p.Asp29Glu (c.87T>G) is ultra-rare (popmax 0.0165%, mid) (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.Asp29Glu (c.87T>G)?

AlphaMissense predicts likely pathogenic (score 0.6096) — an in-silico prediction, not a clinical call.

APC p.Asp29Glu

c.87T>G · rs1561444926 · VCV571834

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6096 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Conditions

familial adenomatous polyposis 1

Computational evidence

Protein change
AlphaMissense	0.6096	likely pathogenic
REVEL	0.205	benign-leaning
⇒ AlphaMissense calls this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.6, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 61 kb · p 0.82 · regional, not allelic
Overall
CADD	25.8	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 0.0165% Middle Eastern · 1/6,058 alleles

Overall 6.84e-05% 1/1,461,562 alleles · ultra-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.Asp29Glu
Coding: c.87T>G
MANE Select: NM_000038
dbSNP: rs1561444926
Type: single nucleotide variant
Location: chr5:112754977 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 29: an α-helix

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

For Familial adenomatous polyposis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Adult
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

APC p.Asp29Val Uncertain significance ★★ same residue
APC p.Gly29= Uncertain significance ★★ same residue
APC p.Asp29= Likely benign ★★ same residue
APC p.Asp29Ala Uncertain significance ★ same residue
APC p.Asp29Gly Uncertain significance ★ same residue
APC p.Asp29His Uncertain significance ★ same residue
APC p.Gly29Asp Uncertain significance ★ same residue
APC p.Gly29Cys Uncertain significance ★ same residue

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-asp29glu (accessed [today's date]).

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