Is FAT4 p.Ile3436Phe (c.10306A>T) pathogenic?

FAT4 p.Ile3436Phe (c.10306A>T) is classified Uncertain significance in FAT4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-12). AlphaMissense: likely benign (0.1271); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with FAT4 p.Ile3436Phe (c.10306A>T)?

FAT4 p.Ile3436Phe (c.10306A>T) is associated with Inborn genetic diseases (ClinVar).

How common is FAT4 p.Ile3436Phe (c.10306A>T) in the general population?

FAT4 p.Ile3436Phe (c.10306A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FAT4 p.Ile3436Phe (c.10306A>T)?

AlphaMissense predicts likely benign (score 0.1271) — an in-silico prediction, not a clinical call.

FAT4 p.Ile3436Phe

c.10306A>T · rs768280436 · VCV2318695

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1271 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1271	likely benign
REVEL	0.1	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 4.6	GERP -2.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 175 kb · p 0.071 · regional, not allelic
Overall
CADD	17.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM I3434F vs ClinVar I3436F) — 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.Ile3436Phe
Coding: c.10306A>T
MANE Select: NM_001291303
dbSNP: rs768280436
Type: single nucleotide variant
Location: chr4:125451316 (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.Ile3436= 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-ile3436phe (accessed [today's date]).

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