Is APC p.Asp328Ala (c.983A>C) pathogenic?

APC p.Asp328Ala (c.983A>C) is classified Uncertain significance in APC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-16). AlphaMissense: likely pathogenic (0.9871); Absent from gnomAD v4.1; Associated with classic or attenuated familial adenomatous polyposis.

What condition is associated with APC p.Asp328Ala (c.983A>C)?

APC p.Asp328Ala (c.983A>C) is associated with classic or attenuated familial adenomatous polyposis (ClinVar).

How common is APC p.Asp328Ala (c.983A>C) in the general population?

APC p.Asp328Ala (c.983A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about APC p.Asp328Ala (c.983A>C)?

AlphaMissense predicts likely pathogenic (score 0.9871) — an in-silico prediction, not a clinical call.

APC p.Asp328Ala

c.983A>C · VCV3386214

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9871 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

classic or attenuated familial adenomatous polyposis

Computational evidence

Protein change
AlphaMissense	0.9871	likely pathogenic · top 7% in APC
REVEL	0.675	pathogenic-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.9, phastCons 1
Regional constraint	o/e 0.33	constrained · MANE · 3,431 bp · p 0.00094 · regional, not allelic
Overall
CADD	28.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

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.Asp328Ala
Coding: c.983A>C
MANE Select: NM_000038
Type: single nucleotide variant
Location: chr5:112819015 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 328: an α-helix

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

Similar variants

APC p.Asp328Gly Uncertain significance ★★ ⚠ same residue
APC p.Asp328Val Uncertain significance ★★ ⚠ same residue
APC p.Asp328= Benign/Likely benign ★★ same residue
APC p.Asp328His Uncertain significance ★ same residue
APC c.1312+3A>G Pathogenic ★★★ same condition
APC p.Arg141Lys Uncertain significance ★★★ same condition
APC p.Arg24Ter Uncertain significance ★★★ same condition
APC p.Arg2816Ter Uncertain significance ★★★ 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-asp328ala (accessed [today's date]).

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