Is FAT2 p.Ala455= (c.1365C>T) pathogenic?

FAT2 p.Ala455= (c.1365C>T) is classified Benign in FAT2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-27). Low-frequency (popmax 4.97%, nfe).

How common is FAT2 p.Ala455= (c.1365C>T) in the general population?

FAT2 p.Ala455= (c.1365C>T) is low-frequency (popmax 4.97%, nfe) (gnomAD).

FAT2 p.Ala455=

c.1365C>T · rs34166097 · VCV1291367

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.97%, 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 -0.051	GERP 0.064, phastCons 0.18
Overall
CADD	4.868	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.97% European (non-Finnish) · 58,701/1,180,004 alleles

Filtering AF 4.94% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.93%

Overall 4.24% 68,412/1,614,126 alleles · low-frequency exomes 63,407/1,461,878 · genomes 5,005/152,248 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	6.83%	15
European (non-Finnish)grpmax	4.97%	20
Remaining individualsnot grpmax-eligible	3.11%	32
Ashkenazi Jewishnot grpmax-eligible	2.43%	41
Admixed American	1.74%	57
South Asian	1.14%	88
Middle Eastern	0.957%	105
African / African-American	0.696%	144
Amishnot grpmax-eligible	0.44%	228
East Asian	0.00891%	11,222

Finnish 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.Ala455=
Coding: c.1365C>T
MANE Select: NM_001447
dbSNP: rs34166097
Type: single nucleotide variant
Location: chr5:151567567 (GRCh38)
Gene constraint: LOEUF 0.554 · pLI <0.01 (gnomAD)
Residue 455: the cadherin 3 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-ala455 (accessed [today's date]).

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