Is APC p.Ala1670= (c.5010T>G) pathogenic?

APC p.Ala1670= (c.5010T>G) is classified Likely benign in APC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-05-16). Very rare (popmax 0.000169%, nfe); Associated with classic or attenuated familial adenomatous polyposis.

How common is APC p.Ala1670= (c.5010T>G) in the general population?

APC p.Ala1670= (c.5010T>G) is very rare (popmax 0.000169%, nfe) (gnomAD).

APC p.Ala1670=

Q: What condition is associated with APC p.Ala1670= (c.5010T>G)?

APC p.Ala1670= (c.5010T>G) is associated with classic or attenuated familial adenomatous polyposis, hereditary neoplastic syndrome (ClinVar).

c.5010T>G · rs1765826793 · VCV2775113

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Conditions

classic or attenuated familial adenomatous polyposis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP 0.55, phastCons 1
Overall
CADD	8.17	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,000 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,614,114 alleles · very rare exomes 2/1,461,806 · genomes 0/152,308 · joint denominator

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.Ala1670=
Coding: c.5010T>G
MANE Select: NM_000038
dbSNP: rs1765826793
Type: single nucleotide variant
Location: chr5:112840604 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1670: the 'disordered' region

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.Ala1670Val Conflicting classifications of pathogenicity ★ 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
APC c.1409-5A>G Likely pathogenic ★★★ same condition
APC c.1626+2T>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-ala1670 (accessed [today's date]).

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