Is FAT1 p.Pro4426Ser (c.13276C>T) pathogenic?

FAT1 p.Pro4426Ser (c.13276C>T) is classified Uncertain significance in FAT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-14). AlphaMissense: ambiguous (0.3456); Very rare (popmax 0.005%, amr); Associated with Inborn genetic diseases.

What condition is associated with FAT1 p.Pro4426Ser (c.13276C>T)?

FAT1 p.Pro4426Ser (c.13276C>T) is associated with Inborn genetic diseases (ClinVar).

How common is FAT1 p.Pro4426Ser (c.13276C>T) in the general population?

FAT1 p.Pro4426Ser (c.13276C>T) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about FAT1 p.Pro4426Ser (c.13276C>T)?

AlphaMissense predicts ambiguous (score 0.3456) — an in-silico prediction, not a clinical call.

FAT1 p.Pro4426Ser

c.13276C>T · rs570007106 · VCV2405145

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3456 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3456	ambiguous
REVEL	0.402	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 25 kb · p 0.00038 · regional, not allelic
Overall
CADD	24.6	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 0.005% Admixed American · 3/60,016 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000372% 6/1,613,916 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,005
East Asian	0.00446%	22,433
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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: FAT1
Protein: p.Pro4426Ser
Coding: c.13276C>T
MANE Select: NM_005245
dbSNP: rs570007106
Type: single nucleotide variant
Location: chr4:186589083 (GRCh38)
Gene constraint: LOEUF 0.571 · pLI <0.01 (gnomAD)

Full FAT1 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

FAT1 p.Ala1663Thr Uncertain significance ★★ same condition
FAT1 p.Ala1862Ser Uncertain significance ★★ ⚠ same condition
FAT1 p.Ala2046Thr Uncertain significance ★★ ⚠ same condition
FAT1 p.Ala2502Asp Uncertain significance ★★ ⚠ same condition
FAT1 p.Ala3007Val Uncertain significance ★★ same condition
FAT1 p.Ala3437Thr Uncertain significance ★★ ⚠ same condition
FAT1 p.Ala3913Ser Uncertain significance ★★ ⚠ same condition
FAT1 p.Ala4042Ser 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/fat1-p-pro4426ser (accessed [today's date]).

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