Is FAT4 p.Pro1844Ser (c.5530C>T) pathogenic?

FAT4 p.Pro1844Ser (c.5530C>T) is classified Conflicting classifications of pathogenicity in FAT4 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-10). AlphaMissense: likely benign (0.0804); Rare (popmax 0.466%, eas); Associated with Inborn genetic diseases.

What condition is associated with FAT4 p.Pro1844Ser (c.5530C>T)?

FAT4 p.Pro1844Ser (c.5530C>T) is associated with Inborn genetic diseases (ClinVar).

How common is FAT4 p.Pro1844Ser (c.5530C>T) in the general population?

FAT4 p.Pro1844Ser (c.5530C>T) is rare (popmax 0.466%, eas) (gnomAD).

What do computational predictors say about FAT4 p.Pro1844Ser (c.5530C>T)?

AlphaMissense predicts likely benign (score 0.0804) — an in-silico prediction, not a clinical call.

FAT4 p.Pro1844Ser

c.5530C>T · rs76963800 · VCV756222

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0804 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.466%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0804	likely benign
REVEL	0.068	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 7.6	GERP 2.5, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 175 kb · p 0.071 · regional, not allelic
Overall
CADD	15.99	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 0.466% East Asian · 209/44,836 alleles

Filtering AF 0.414% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.394%

Overall 0.0131% 212/1,613,612 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.466%	215
Remaining individualsnot grpmax-eligible	0.0032%	31,247
South Asian	0.0011%	91,074

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.Pro1844Ser
Coding: c.5530C>T
MANE Select: NM_001291303
dbSNP: rs76963800
Type: single nucleotide variant
Location: chr4:125407102 (GRCh38)
Gene constraint: LOEUF 0.317 · pLI 1.00 (gnomAD)
Residue 1844: the cadherin 18 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.Pro1844= 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-pro1844ser (accessed [today's date]).

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