Is FAT2 p.Pro956= (c.2868C>T) pathogenic?

FAT2 p.Pro956= (c.2868C>T) is classified Likely benign in FAT2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-23). Very rare (popmax 0.00788%, nfe).

How common is FAT2 p.Pro956= (c.2868C>T) in the general population?

FAT2 p.Pro956= (c.2868C>T) is very rare (popmax 0.00788%, nfe) (gnomAD).

FAT2 p.Pro956=

c.2868C>T · rs374807522 · VCV746757

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00788%, 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 0.03	GERP -4.4, phastCons 0.062
Overall
CADD	6.473	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00788% European (non-Finnish) · 93/1,180,026 alleles

Filtering AF 0.00656% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00608%

Overall 0.00638% 103/1,613,990 alleles · very rare exomes 96/1,461,864 · genomes 7/152,126 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00788%	12,688
Admixed American	0.005%	19,999
South Asian	0.00329%	30,359
Finnishnot grpmax-eligible	0.00312%	32,006
Remaining individualsnot grpmax-eligible	0.0016%	62,486
African / African-American	0.00133%	74,910

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.Pro956=
Coding: c.2868C>T
MANE Select: NM_001447
dbSNP: rs374807522
Type: single nucleotide variant
Location: chr5:151566064 (GRCh38)
Gene constraint: LOEUF 0.554 · pLI <0.01 (gnomAD)
Residue 956: the cadherin 8 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-pro956 (accessed [today's date]).

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