Is FAT2 p.Arg1097Pro (c.3290G>C) pathogenic?

FAT2 p.Arg1097Pro (c.3290G>C) is classified Uncertain significance in FAT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-21). AlphaMissense: likely pathogenic (0.843); Very rare (popmax 8.47e-05%, nfe).

How common is FAT2 p.Arg1097Pro (c.3290G>C) in the general population?

FAT2 p.Arg1097Pro (c.3290G>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about FAT2 p.Arg1097Pro (c.3290G>C)?

AlphaMissense predicts likely pathogenic (score 0.843) — an in-silico prediction, not a clinical call.

FAT2 p.Arg1097Pro

c.3290G>C · VCV4752109

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.843 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Computational evidence

Protein change
AlphaMissense	0.843	likely pathogenic · top 9% in FAT2
REVEL	0.41	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 28 kb · p 7.9e-10 · regional, not allelic
Overall
CADD	27.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,046 alleles

Overall 6.2e-05% 1/1,614,012 alleles · very rare exomes 0/1,461,848 · genomes 1/152,164 · joint denominator

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: FAT2
Protein: p.Arg1097Pro
Coding: c.3290G>C
MANE Select: NM_001447
Type: single nucleotide variant
Location: chr5:151563609 (GRCh38)
Gene constraint: LOEUF 0.554 · pLI <0.01 (gnomAD)
Residue 1097: the cadherin 9 domain

Full FAT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FAT2 p.Arg1097Gln Uncertain significance ★★ ⚠ same residue
FAT2 p.Ala1009Val Uncertain significance ★★ ⚠ same type
FAT2 p.Ala1078Thr Uncertain significance ★★ ⚠ same type
FAT2 p.Ala1079Asp Uncertain significance ★★ ⚠ same type
FAT2 p.Ala1975Glu Uncertain significance ★★ same type
FAT2 p.Ala2491Glu Uncertain significance ★★ same type
FAT2 p.Ala249Val Uncertain significance ★★ ⚠ same type
FAT2 p.Ala2587Val Uncertain significance ★★ 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/fat2-p-arg1097pro (accessed [today's date]).

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