Is FAT4 p.Asp1920= (c.5760T>C) pathogenic?

FAT4 p.Asp1920= (c.5760T>C) is classified Benign in FAT4 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). Common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele; Associated with van Maldergem syndrome 2.

What condition is associated with FAT4 p.Asp1920= (c.5760T>C)?

FAT4 p.Asp1920= (c.5760T>C) is associated with van Maldergem syndrome 2, Hennekam lymphangiectasia-lymphedema syndrome 2 (ClinVar).

FAT4 p.Asp1920=

Q: How common is FAT4 p.Asp1920= (c.5760T>C) in the general population?

FAT4 p.Asp1920= (c.5760T>C) is common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.5760T>C · rs958415 · VCV380250

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

van Maldergem syndrome 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.39 · evaluated, not missing
Constraint at this position
Conservation	phyloP -6.6	GERP -4.7
Overall
CADD	0.253	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 100% East Asian · 44,751/44,754 alleles

Filtering AF 99.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 99.7%

Overall 99.8% 1,608,114/1,612,062 alleles · common exomes 1,457,580/1,460,120 · genomes 150,534/151,942 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	100%	1
Finnishnot grpmax-eligible	100%	1
East Asiangrpmax	100%	1
South Asian	100%	1
European (non-Finnish)	99.9%	1
Ashkenazi Jewishnot grpmax-eligible	99.9%	1
Remaining individualsnot grpmax-eligible	99.6%	1
Admixed American	99.3%	1
Middle Eastern	99.3%	1
African / African-American	97.2%	1

Amish 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: FAT4
Protein: p.Asp1920=
Coding: c.5760T>C
MANE Select: NM_001291303
dbSNP: rs958415
Type: single nucleotide variant
Location: chr4:125408634 (GRCh38)
Gene constraint: LOEUF 0.317 · pLI 1.00 (gnomAD)
Residue 1920: the cadherin 18 domain

Full FAT4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

van Maldergem syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Hennekam lymphangiectasia-lymphedema syndrome 2

Similar variants

FAT4 p.Arg1902Ter Pathogenic/Likely pathogenic ★★ same condition
FAT4 p.Gln4530Ter Pathogenic/Likely pathogenic ★★ same condition
FAT4 c.5307+6T>A Uncertain significance ★★ same condition
FAT4 c.6843+4A>G Uncertain significance ★★ same condition
FAT4 p.Ala132Asp Uncertain significance ★★ ⚠ same condition
FAT4 p.Ala1984Thr Uncertain significance ★★ ⚠ same condition
FAT4 p.Ala198Val Uncertain significance ★★ same condition
FAT4 p.Ala2210= Uncertain significance ★★ same condition

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/fat4-p-asp1920 (accessed [today's date]).

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