Is FAT4 p.Pro4591Arg (c.13772C>G) pathogenic?

FAT4 p.Pro4591Arg (c.13772C>G) is classified Uncertain significance in FAT4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: likely pathogenic (0.9428); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with FAT4 p.Pro4591Arg (c.13772C>G)?

FAT4 p.Pro4591Arg (c.13772C>G) is associated with Inborn genetic diseases (ClinVar).

How common is FAT4 p.Pro4591Arg (c.13772C>G) in the general population?

FAT4 p.Pro4591Arg (c.13772C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FAT4 p.Pro4591Arg (c.13772C>G)?

AlphaMissense predicts likely pathogenic (score 0.9428) — an in-silico prediction, not a clinical call.

FAT4 p.Pro4591Arg

c.13772C>G · VCV4619794

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9428 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9428	likely pathogenic
REVEL	0.545	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.6	GERP 1.4, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 175 kb · p 0.071 · regional, not allelic
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P4589R vs ClinVar P4591R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FAT4
Protein: p.Pro4591Arg
Coding: c.13772C>G
MANE Select: NM_001291303
Type: single nucleotide variant
Location: chr4:125490588 (GRCh38)
Gene constraint: LOEUF 0.317 · pLI 1.00 (gnomAD)

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.Pro4591= Likely benign ★★ 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-pro4591arg (accessed [today's date]).

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