Is APC2 p.Pro335= (c.1005A>T) pathogenic?

APC2 p.Pro335= (c.1005A>T) is classified Likely benign in APC2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-09). No allele count reported in gnomAD v4.1 (AN 1,528,338); Associated with APC2-related disorder.

What condition is associated with APC2 p.Pro335= (c.1005A>T)?

APC2 p.Pro335= (c.1005A>T) is associated with APC2-related disorder (ClinVar).

How common is APC2 p.Pro335= (c.1005A>T) in the general population?

APC2 p.Pro335= (c.1005A>T) is no allele count reported in gnomAD v4.1 (AN 1,528,338) (gnomAD).

APC2 p.Pro335=

c.1005A>T · rs2083841910 · VCV3034654

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,528,338)

Conditions

APC2-related disorder

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 -15	GERP -3.5
Overall
CADD	0.056	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,528,338). 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: APC2
Protein: p.Pro335=
Coding: c.1005A>T
MANE Select: NM_005883
dbSNP: rs2083841910
Type: single nucleotide variant
Location: chr19:1457041 (GRCh38)
Gene constraint: LOEUF 0.961 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 48.87
Residue 335: a UniProt-annotated variant site (in cdcbm10)

Full APC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

APC2-related disorder

Similar variants

APC2 p.Pro335Leu Uncertain significance ★ ⚠ same residue
APC2 p.Arg853Pro Uncertain significance ★★ ⚠ same condition
APC2 p.Gln1000Lys Uncertain significance ★★ ⚠ same condition
APC2 p.Pro1253Ser Uncertain significance ★★ ⚠ same condition
APC2 p.Pro2066Ala Uncertain significance ★★ ⚠ same condition
APC2 p.Arg1602Trp Uncertain significance ★ ⚠ same condition
APC2 p.Leu283= Conflicting classifications of pathogenicity ★ same condition
APC2 p.Ser1861Asn 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/apc2-p-pro335 (accessed [today's date]).

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