Is FAT2 p.Phe1602Ser (c.4805T>C) pathogenic?

FAT2 p.Phe1602Ser (c.4805T>C) is classified Benign/Likely benign in FAT2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-19). AlphaMissense: likely benign (0.14); Low-frequency (popmax 1.09%, afr).

How common is FAT2 p.Phe1602Ser (c.4805T>C) in the general population?

FAT2 p.Phe1602Ser (c.4805T>C) is low-frequency (popmax 1.09%, afr) (gnomAD).

What do computational predictors say about FAT2 p.Phe1602Ser (c.4805T>C)?

AlphaMissense predicts likely benign (score 0.14) — an in-silico prediction, not a clinical call.

FAT2 p.Phe1602Ser

c.4805T>C · rs116401802 · VCV716119

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.14 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.09%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.14	likely benign
REVEL	0.154	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.5	GERP 2, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 28 kb · p 7.9e-10 · regional, not allelic
Overall
CADD	19.84	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 1.09% African / African-American · 821/75,006 alleles

Filtering AF 1.03% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.01%

Overall 0.0551% 889/1,612,610 alleles · low-frequency exomes 442/1,460,296 · genomes 447/152,314 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.09%	91
Admixed American	0.0517%	1,935
Remaining individualsnot grpmax-eligible	0.0464%	2,155
South Asian	0.0011%	90,948
European (non-Finnish)	0.000594%	168,472

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.Phe1602Ser
Coding: c.4805T>C
MANE Select: NM_001447
dbSNP: rs116401802
Type: single nucleotide variant
Location: chr5:151546322 (GRCh38)
Gene constraint: LOEUF 0.554 · pLI <0.01 (gnomAD)
Residue 1602: the cadherin 14 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-phe1602ser (accessed [today's date]).

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