Is GALNT12 p.Phe488= (c.1464C>T) pathogenic?

GALNT12 p.Phe488= (c.1464C>T) is classified Benign/Likely benign in GALNT12 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-04-27). Ultra-rare (popmax 0.0107%, afr); Associated with colorectal cancer, susceptibility to, 1.

What condition is associated with GALNT12 p.Phe488= (c.1464C>T)?

GALNT12 p.Phe488= (c.1464C>T) is associated with colorectal cancer, susceptibility to, 1 (ClinVar).

How common is GALNT12 p.Phe488= (c.1464C>T) in the general population?

GALNT12 p.Phe488= (c.1464C>T) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

GALNT12 p.Phe488=

c.1464C>T · rs772731021 · VCV1080834

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Conditions

colorectal cancer, susceptibility to, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -11	GERP -3.6
Overall
CADD	5.647	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0107% African / African-American · 8/74,890 alleles

Filtering AF 0.00528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.00112% 18/1,613,948 alleles · ultra-rare exomes 12/1,461,842 · genomes 6/152,106 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0107%	9,361
East Asian	0.00223%	44,888
Admixed American	0.00167%	59,986
European (non-Finnish)	0.000678%	147,499

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: GALNT12
Protein: p.Phe488=
Coding: c.1464C>T
MANE Select: NM_024642
dbSNP: rs772731021
Type: single nucleotide variant
Location: chr9:98845982 (GRCh38)
Gene constraint: LOEUF 1.054 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 93.84 · 1 PDB
Residue 488: the ricin b-type lectin domain; a β-strand

Full GALNT12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

colorectal cancer, susceptibility to, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GALNT12 p.Phe488Cys Uncertain significance ★★ ⚠ same residue
GALNT12 p.Phe488Leu Uncertain significance ★ ⚠ same residue
GALNT12 c.918-2A>C Uncertain significance ★★ same condition
GALNT12 p.Ala148Ser Uncertain significance ★★ same condition
GALNT12 p.Ala148Val Uncertain significance ★★ ⚠ same condition
GALNT12 p.Ala211Thr Uncertain significance ★★ ⚠ same condition
GALNT12 p.Ala219Val Uncertain significance ★★ ⚠ same condition
GALNT12 p.Ala29Thr 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/galnt12-p-phe488 (accessed [today's date]).

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