Is FAT4 p.Ser1985= (c.5955A>C) pathogenic?

FAT4 p.Ser1985= (c.5955A>C) is classified Conflicting classifications of pathogenicity in FAT4 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-07-29). Very rare (popmax 0.00895%, eas); Associated with Hennekam lymphangiectasia-lymphedema syndrome 2.

What condition is associated with FAT4 p.Ser1985= (c.5955A>C)?

FAT4 p.Ser1985= (c.5955A>C) is associated with Hennekam lymphangiectasia-lymphedema syndrome 2, van Maldergem syndrome 2 (ClinVar).

How common is FAT4 p.Ser1985= (c.5955A>C) in the general population?

FAT4 p.Ser1985= (c.5955A>C) is very rare (popmax 0.00895%, eas) (gnomAD).

FAT4 p.Ser1985=

c.5955A>C · rs770793156 · VCV2998279

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00895%, eas)

Conditions

Hennekam lymphangiectasia-lymphedema syndrome 2

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 -2.5	GERP -4.1
Overall
CADD	1.104	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00895% East Asian · 4/44,684 alleles

Filtering AF 0.00299% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00181%

Overall 0.000373% 6/1,607,884 alleles · very rare exomes 5/1,455,706 · genomes 1/152,178 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00895%	11,171
Remaining individualsnot grpmax-eligible	0.00322%	31,101

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.Ser1985=
Coding: c.5955A>C
MANE Select: NM_001291303
dbSNP: rs770793156
Type: single nucleotide variant
Location: chr4:125414918 (GRCh38)
Gene constraint: LOEUF 0.317 · pLI 1.00 (gnomAD)
Residue 1985: the cadherin 19 domain

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

Disease context

Hennekam lymphangiectasia-lymphedema syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: van Maldergem 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-ser1985 (accessed [today's date]).

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