Is APC p.Pro1319Ser (c.3955C>T) pathogenic?

APC p.Pro1319Ser (c.3955C>T) is classified Uncertain significance in APC (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-16). AlphaMissense: likely benign (0.0618); Absent from gnomAD v4.1.

How common is APC p.Pro1319Ser (c.3955C>T) in the general population?

APC p.Pro1319Ser (c.3955C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about APC p.Pro1319Ser (c.3955C>T)?

AlphaMissense predicts likely benign (score 0.0618) — an in-silico prediction, not a clinical call.

APC p.Pro1319Ser

c.3955C>T · rs1765567515 · VCV2444628

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0618 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0618	likely benign
REVEL	0.203	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 0.33	GERP -2.3, phastCons 0.023
Regional constraint	o/e 1.09	unconstrained · MANE · 1,681 bp · p 0.023 · regional, not allelic
Overall
CADD	3.09	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

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.Pro1319Ser
Coding: c.3955C>T
MANE Select: NM_000038
dbSNP: rs1765567515
Type: single nucleotide variant
Location: chr5:112839549 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1319: the 'responsible for down-regulation through a process mediated by direct ubiquitination' region; the 'disordered' region

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

Similar variants

APC p.Pro1319Ala Uncertain significance ★★ ⚠ same residue
APC p.Pro1319Leu Uncertain significance ★★ same residue
APC p.Pro1319Thr Uncertain significance ★★ ⚠ same residue
APC p.Pro1319= Likely benign ★ same residue
APC p.Pro1319fs Pathogenic/Likely pathogenic ★★ same residue
APC p.Pro1319_Val1320insTer Pathogenic ★ same residue
APC c.1312+3A>C Likely pathogenic ★★★ same type
APC c.1312+3A>G Pathogenic ★★★ same type

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-pro1319ser (accessed [today's date]).

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