Is APC p.Val754= (c.2262T>G) pathogenic?

APC p.Val754= (c.2262T>G) is classified Benign/Likely benign in APC (ClinVar, Multiple submitters, 20 submitters; last evaluated 2026-01-28). Rare (popmax 0.32%, afr); Associated with classic or attenuated familial adenomatous polyposis.

What condition is associated with APC p.Val754= (c.2262T>G)?

APC p.Val754= (c.2262T>G) is associated with classic or attenuated familial adenomatous polyposis, hereditary neoplastic syndrome, familial adenomatous polyposis 1 (ClinVar).

How common is APC p.Val754= (c.2262T>G) in the general population?

APC p.Val754= (c.2262T>G) is rare (popmax 0.32%, afr) (gnomAD).

APC p.Val754=

c.2262T>G · rs148987776 · VCV135687

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 20 submitters

gnomAD v4.1

Rare

rare (popmax 0.32%, afr)

Conditions

classic or attenuated familial adenomatous polyposis

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 -0.36	GERP -5.5, phastCons 0.19
Overall
CADD	1.611	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.32% African / African-American · 240/75,022 alleles

Filtering AF 0.287% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.274%

Overall 0.0182% 293/1,614,044 alleles · rare exomes 154/1,461,770 · genomes 139/152,274 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.32%	313
Remaining individualsnot grpmax-eligible	0.0176%	5,682
Middle Eastern	0.0165%	6,062
Admixed American	0.00833%	12,004
European (non-Finnish)	0.00297%	33,715
South Asian	0.0011%	91,082

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: APC
Protein: p.Val754=
Coding: c.2262T>G
MANE Select: NM_000038
dbSNP: rs148987776
Type: single nucleotide variant
Location: chr5:112837856 (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

classic or attenuated familial adenomatous polyposis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome familial adenomatous polyposis 1

Similar variants

APC p.Val754Ile Uncertain significance ★★ same residue
APC p.Val754Phe Uncertain significance ★★ 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
APC c.1409-5A>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-val754 (accessed [today's date]).

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