Is FAT1 p.Phe615= (c.1845T>C) pathogenic?

FAT1 p.Phe615= (c.1845T>C) is classified Benign/Likely benign in FAT1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-02). Low-frequency (popmax 3.8%, nfe).

How common is FAT1 p.Phe615= (c.1845T>C) in the general population?

FAT1 p.Phe615= (c.1845T>C) is low-frequency (popmax 3.8%, nfe) (gnomAD).

FAT1 p.Phe615=

c.1845T>C · rs4862726 · VCV1225235

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.8%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.2	GERP -5.4
Overall
CADD	0.454	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.8% European (non-Finnish) · 44,844/1,179,856 alleles

Filtering AF 3.77% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.76%

Overall 3.53% 57,017/1,613,898 alleles · low-frequency exomes 52,340/1,461,626 · genomes 4,677/152,272 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	9.53%	10
European (non-Finnish)grpmax	3.8%	26
Amishnot grpmax-eligible	3.73%	27
Remaining individualsnot grpmax-eligible	2.9%	34
East Asian	2.67%	37
Admixed American	2.29%	44
Ashkenazi Jewishnot grpmax-eligible	1.24%	80
South Asian	0.859%	116
Middle Eastern	0.825%	121
African / African-American	0.605%	165

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: FAT1
Protein: p.Phe615=
Coding: c.1845T>C
MANE Select: NM_005245
dbSNP: rs4862726
Type: single nucleotide variant
Location: chr4:186707983 (GRCh38)
Gene constraint: LOEUF 0.571 · pLI <0.01 (gnomAD)
Residue 615: the cadherin 5 domain

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

Similar variants

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
FAT1 p.Ala3007Val Uncertain significance ★★ same type
FAT1 p.Ala3437Thr 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-phe615 (accessed [today's date]).

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