Is FAT2 p.Phe1763Ser (c.5288T>C) pathogenic?

FAT2 p.Phe1763Ser (c.5288T>C) is classified Uncertain significance in FAT2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-15). AlphaMissense: likely benign (0.302); Very rare (popmax 0.01%, amr).

How common is FAT2 p.Phe1763Ser (c.5288T>C) in the general population?

FAT2 p.Phe1763Ser (c.5288T>C) is very rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about FAT2 p.Phe1763Ser (c.5288T>C)?

AlphaMissense predicts likely benign (score 0.302) — an in-silico prediction, not a clinical call.

FAT2 p.Phe1763Ser

c.5288T>C · rs767054653 · VCV2072861

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.302 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.01%, amr)

Computational evidence

Protein change
AlphaMissense	0.302	likely benign
REVEL	0.483	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.1	GERP 1.1, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 28 kb · p 7.9e-10 · regional, not allelic
Overall
CADD	25.0	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 0.01% Admixed American · 6/60,008 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.000434% 7/1,614,124 alleles · very rare exomes 6/1,461,886 · genomes 1/152,238 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	10,001
Remaining individualsnot grpmax-eligible	0.0016%	62,490

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.Phe1763Ser
Coding: c.5288T>C
MANE Select: NM_001447
dbSNP: rs767054653
Type: single nucleotide variant
Location: chr5:151545839 (GRCh38)
Gene constraint: LOEUF 0.554 · pLI <0.01 (gnomAD)
Residue 1763: the cadherin 16 domain

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

Similar variants

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
FAT2 p.Ala2618Thr 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-phe1763ser (accessed [today's date]).

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