Is FAT1 p.Pro4411= (c.13233C>T) pathogenic?

FAT1 p.Pro4411= (c.13233C>T) is classified Benign/Likely benign in FAT1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-02). Common (popmax 18.2%, eas) — too common for a highly-penetrant pathogenic allele.

FAT1 p.Pro4411=

Q: How common is FAT1 p.Pro4411= (c.13233C>T) in the general population?

FAT1 p.Pro4411= (c.13233C>T) is common (popmax 18.2%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.13233C>T · rs3775307 · VCV1227642

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 18.2%, eas) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.071	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.87	GERP -2.2
Overall
CADD	3.347	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 18.2% East Asian · 8,169/44,854 alleles

Filtering AF 17.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 17.7%

Overall 3.87% 62,390/1,613,762 alleles · common exomes 56,800/1,461,688 · genomes 5,590/152,074 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	18.2%	5
Admixed American	12.9%	8
Finnishnot grpmax-eligible	7.29%	14
Amishnot grpmax-eligible	4.61%	22
Remaining individualsnot grpmax-eligible	3.72%	27
European (non-Finnish)	3.19%	31
South Asian	1.22%	82
African / African-American	0.699%	143
Middle Eastern	0.627%	160
Ashkenazi Jewishnot grpmax-eligible	0.611%	164

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.Pro4411=
Coding: c.13233C>T
MANE Select: NM_005245
dbSNP: rs3775307
Type: single nucleotide variant
Location: chr4:186589126 (GRCh38)
Gene constraint: LOEUF 0.571 · pLI <0.01 (gnomAD)

Full FAT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FAT1 p.Pro4411Ser Uncertain significance ★ same residue
FAT1 p.Pro4411Thr Uncertain significance ★ ⚠ same residue
FAT1 p.Ala1663Thr Uncertain significance ★★ same type
FAT1 p.Ala1762Val Uncertain significance ★★ ⚠ same type
FAT1 p.Ala1862Ser Uncertain significance ★★ ⚠ same type
FAT1 p.Ala2046Thr Uncertain significance ★★ ⚠ same type
FAT1 p.Ala2456Thr Uncertain significance ★★ ⚠ same type
FAT1 p.Ala2502Asp Uncertain significance ★★ ⚠ same type

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-pro4411 (accessed [today's date]).

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