Is APC p.Ser130= (c.390T>C) pathogenic?

APC p.Ser130= (c.390T>C) is classified Benign/Likely benign in APC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-23). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with APC p.Ser130= (c.390T>C)?

APC p.Ser130= (c.390T>C) is associated with hereditary neoplastic syndrome, familial adenomatous polyposis 1 (ClinVar).

How common is APC p.Ser130= (c.390T>C) in the general population?

APC p.Ser130= (c.390T>C) is absent from gnomAD v4.1 (gnomAD).

APC p.Ser130=

c.390T>C · rs1561464982 · VCV631416

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

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 0.88	phastCons 1
Overall
CADD	9.258	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.Ser130=
Coding: c.390T>C
MANE Select: NM_000038
dbSNP: rs1561464982
Type: single nucleotide variant
Location: chr5:112767358 (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

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

Also linked: familial adenomatous polyposis 1

Similar variants

APC p.Ser130Cys Uncertain significance ★★ same residue
APC p.Ser130Ile Uncertain significance ★★ same residue
APC p.Ser130Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
APC p.Ser130Asn Likely benign ★ same residue
APC p.Ser130fs Pathogenic/Likely pathogenic ★★ 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-ser130 (accessed [today's date]).

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