Is FAT2 p.Pro3887= (c.11661C>T) pathogenic?

FAT2 p.Pro3887= (c.11661C>T) is classified Likely benign in FAT2 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-07-01). Ultra-rare (popmax 0.0107%, nfe).

How common is FAT2 p.Pro3887= (c.11661C>T) in the general population?

FAT2 p.Pro3887= (c.11661C>T) is ultra-rare (popmax 0.0107%, nfe) (gnomAD).

FAT2 p.Pro3887=

c.11661C>T · rs375099975 · VCV3058510

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.9	GERP -3.8
Overall
CADD	0.071	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0107% European (non-Finnish) · 126/1,180,046 alleles

Filtering AF 0.00911% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00855%

Overall 0.00855% 138/1,614,090 alleles · ultra-rare exomes 131/1,461,892 · genomes 7/152,198 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0144%	6,943
European (non-Finnish)grpmax	0.0107%	9,365
Admixed American	0.00167%	60,004
African / African-American	0.00133%	74,914
South Asian	0.0011%	91,086

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: FAT2
Protein: p.Pro3887=
Coding: c.11661C>T
MANE Select: NM_001447
dbSNP: rs375099975
Type: single nucleotide variant
Location: chr5:151512409 (GRCh38)
Gene constraint: LOEUF 0.554 · pLI <0.01 (gnomAD)
Residue 3887: the laminin g-like domain

Full FAT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FAT2 p.Ala1009Val Uncertain significance ★★ ⚠ same type
FAT2 p.Ala1078Thr Uncertain significance ★★ ⚠ same type
FAT2 p.Ala1079Asp Uncertain significance ★★ ⚠ same type
FAT2 p.Ala1975Glu Uncertain significance ★★ same type
FAT2 p.Ala2491Glu Uncertain significance ★★ same type
FAT2 p.Ala249Val Uncertain significance ★★ ⚠ same type
FAT2 p.Ala2587Val Uncertain significance ★★ same type
FAT2 p.Ala2618Thr 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/fat2-p-pro3887 (accessed [today's date]).

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