Is FAT4 p.Val973= (c.2919C>T) pathogenic?

FAT4 p.Val973= (c.2919C>T) is classified Benign in FAT4 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-05). Low-frequency (popmax 3.35%, eas); Associated with van Maldergem syndrome 2.

What condition is associated with FAT4 p.Val973= (c.2919C>T)?

FAT4 p.Val973= (c.2919C>T) is associated with van Maldergem syndrome 2, Hennekam lymphangiectasia-lymphedema syndrome 2 (ClinVar).

How common is FAT4 p.Val973= (c.2919C>T) in the general population?

FAT4 p.Val973= (c.2919C>T) is low-frequency (popmax 3.35%, eas) (gnomAD).

FAT4 p.Val973=

c.2919C>T · rs144356360 · VCV670933

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.35%, eas)

Conditions

van Maldergem 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 -3.3	GERP -4.7
Overall
CADD	0.201	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.35% East Asian · 1,505/44,868 alleles

Filtering AF 3.21% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.16%

Overall 0.113% 1,818/1,613,726 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	3.35%	30
Finnishnot grpmax-eligible	0.203%	491
Remaining individualsnot grpmax-eligible	0.0816%	1,226
South Asian	0.0483%	2,070
European (non-Finnish)	0.00729%	13,718
Admixed American	0.00333%	30,011

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.Val973=
Coding: c.2919C>T
MANE Select: NM_001291303
dbSNP: rs144356360
Type: single nucleotide variant
Location: chr4:125319330 (GRCh38)
Gene constraint: LOEUF 0.317 · pLI 1.00 (gnomAD)
Residue 973: the cadherin 9 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.Val973Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-val973 (accessed [today's date]).

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