Is APC p.Ala783Ser (c.2347G>T) pathogenic?

APC p.Ala783Ser (c.2347G>T) is classified Uncertain significance in APC (ClinVar, No assertion criteria, 1 submitter; last evaluated 2014-06-11). AlphaMissense: likely benign (0.0893); No allele count reported in gnomAD v4.1 (AN 1,613,974); Associated with familial adenomatous polyposis 1.

What condition is associated with APC p.Ala783Ser (c.2347G>T)?

APC p.Ala783Ser (c.2347G>T) is associated with familial adenomatous polyposis 1 (ClinVar).

How common is APC p.Ala783Ser (c.2347G>T) in the general population?

APC p.Ala783Ser (c.2347G>T) is no allele count reported in gnomAD v4.1 (AN 1,613,974) (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.Ala783Ser (c.2347G>T)?

AlphaMissense predicts likely benign (score 0.0893) — an in-silico prediction, not a clinical call.

APC p.Ala783Ser

c.2347G>T · rs587780590 · VCV135688

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0893 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,974)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

familial adenomatous polyposis 1

Computational evidence

Protein change
AlphaMissense	0.0893	likely benign
REVEL	0.252	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP 0.29, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 256 bp · p 0.22 · regional, not allelic
Overall
CADD	19.08	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

No allele count reported in gnomAD v4.1 (AN 1,613,974). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: APC
Protein: p.Ala783Ser
Coding: c.2347G>T
MANE Select: NM_000038
dbSNP: rs587780590
Type: single nucleotide variant
Location: chr5:112837941 (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

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.Ala783Thr Uncertain significance ★★ ⚠ same residue
APC p.Ala783Val Uncertain significance ★★ same residue
APC p.Ala783= Benign/Likely benign ★★ 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-ala783ser (accessed [today's date]).

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