Is APC p.Ala501= (c.1503T>A) pathogenic?

APC p.Ala501= (c.1503T>A) is classified Likely benign in APC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-30). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with APC p.Ala501= (c.1503T>A)?

APC p.Ala501= (c.1503T>A) is associated with hereditary neoplastic syndrome (ClinVar).

How common is APC p.Ala501= (c.1503T>A) in the general population?

APC p.Ala501= (c.1503T>A) is absent from gnomAD v4.1 (gnomAD).

APC p.Ala501=

c.1503T>A · VCV4121685

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

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 1.4	GERP -1.9, phastCons 1
Overall
CADD	11.14	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: APC
Protein: p.Ala501=
Coding: c.1503T>A
MANE Select: NM_000038
Type: single nucleotide variant
Location: chr5:112827202 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 501: an α-helix

Full APC gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

APC p.Ala501Asp Uncertain significance ★★ ⚠ same residue
APC p.Ala501Ser Uncertain significance ★★ same residue
APC p.Ala501Thr Uncertain significance ★★ same residue
APC p.Ala501Val Uncertain significance ★★ ⚠ same residue
APC p.Ala501Gly 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

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-ala501 (accessed [today's date]).

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