Is FAT4 p.Pro193= (c.579G>A) pathogenic?

FAT4 p.Pro193= (c.579G>A) is classified Likely benign in FAT4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-10). Very rare (popmax 0.000254%, nfe); Associated with Inborn genetic diseases.

What condition is associated with FAT4 p.Pro193= (c.579G>A)?

FAT4 p.Pro193= (c.579G>A) is associated with Inborn genetic diseases (ClinVar).

How common is FAT4 p.Pro193= (c.579G>A) in the general population?

FAT4 p.Pro193= (c.579G>A) is very rare (popmax 0.000254%, nfe) (gnomAD).

FAT4 p.Pro193=

c.579G>A · VCV3669245

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.4	GERP -4.4
Overall
CADD	7.335	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,180,026 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000342% 5/1,461,688 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,252
European (non-Finnish)grpmax	0.000254%	393,342

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro193=
Coding: c.579G>A
MANE Select: NM_001291303
Type: single nucleotide variant
Location: chr4:125316990 (GRCh38)
Gene constraint: LOEUF 0.317 · pLI 1.00 (gnomAD)
Residue 193: 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.Pro193Leu Uncertain significance ★ same residue
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

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-pro193 (accessed [today's date]).

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