Is FAT4 p.Ser173Phe (c.518C>T) pathogenic?

FAT4 p.Ser173Phe (c.518C>T) is classified Uncertain significance in FAT4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-17). AlphaMissense: likely pathogenic (0.6701); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with FAT4 p.Ser173Phe (c.518C>T)?

FAT4 p.Ser173Phe (c.518C>T) is associated with Inborn genetic diseases (ClinVar).

How common is FAT4 p.Ser173Phe (c.518C>T) in the general population?

FAT4 p.Ser173Phe (c.518C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about FAT4 p.Ser173Phe (c.518C>T)?

AlphaMissense predicts likely pathogenic (score 0.6701) — an in-silico prediction, not a clinical call.

FAT4 p.Ser173Phe

c.518C>T · rs2530421271 · VCV2277806

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6701 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6701	likely pathogenic
REVEL	0.264	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense calls this damaging; REVEL does not; SaProt makes no call.
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 0.98	unconstrained · MANE · 175 kb · p 0.071 · regional, not allelic
Overall
CADD	27.7	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 0.00167% Admixed American · 1/60,032 alleles

Overall 6.84e-05% 1/1,461,678 alleles · very rare

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: FAT4
Protein: p.Ser173Phe
Coding: c.518C>T
MANE Select: NM_001291303
dbSNP: rs2530421271
Type: single nucleotide variant
Location: chr4:125316929 (GRCh38)
Gene constraint: LOEUF 0.317 · pLI 1.00 (gnomAD)
Residue 173: the cadherin 2 domain

Full FAT4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FAT4 p.Ala1020Val Uncertain significance ★★ same condition
FAT4 p.Ala1032Val Uncertain significance ★★ ⚠ same condition
FAT4 p.Ala1194Thr Uncertain significance ★★ ⚠ same condition
FAT4 p.Ala132Asp Uncertain significance ★★ ⚠ same condition
FAT4 p.Ala1536Ser Uncertain significance ★★ ⚠ same condition
FAT4 p.Ala1783Thr Uncertain significance ★★ ⚠ same condition
FAT4 p.Ala1783Val Uncertain significance ★★ ⚠ same condition
FAT4 p.Ala198Val 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/fat4-p-ser173phe (accessed [today's date]).

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