Is FAT2 p.Phe1099Ser (c.3296T>C) pathogenic?

FAT2 p.Phe1099Ser (c.3296T>C) is classified Benign/Likely benign in FAT2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-13). AlphaMissense: likely benign (0.0934); Rare (popmax 0.24%, afr).

How common is FAT2 p.Phe1099Ser (c.3296T>C) in the general population?

FAT2 p.Phe1099Ser (c.3296T>C) is rare (popmax 0.24%, afr) (gnomAD).

What do computational predictors say about FAT2 p.Phe1099Ser (c.3296T>C)?

AlphaMissense predicts likely benign (score 0.0934) — an in-silico prediction, not a clinical call.

FAT2 p.Phe1099Ser

c.3296T>C · rs141548933 · VCV2084208

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0934 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.24%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0934	likely benign
REVEL	0.046	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP -0.62, phastCons 0.31
Regional constraint	o/e 0.90	unconstrained · MANE · 28 kb · p 7.9e-10 · regional, not allelic
Overall
CADD	9.994	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 0.24% African / African-American · 180/75,052 alleles

Filtering AF 0.211% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.2%

Overall 0.0119% 192/1,614,170 alleles · rare exomes 82/1,461,864 · genomes 110/152,306 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.24%	417
Remaining individualsnot grpmax-eligible	0.0112%	8,929
Admixed American	0.00666%	15,005
European (non-Finnish)	8.47e-05%	1,180,030

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.Phe1099Ser
Coding: c.3296T>C
MANE Select: NM_001447
dbSNP: rs141548933
Type: single nucleotide variant
Location: chr5:151563603 (GRCh38)
Gene constraint: LOEUF 0.554 · pLI <0.01 (gnomAD)
Residue 1099: the cadherin 9 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-phe1099ser (accessed [today's date]).

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