Is FLT4 p.Arg82Ter (c.244C>T) pathogenic?

FLT4 p.Arg82Ter (c.244C>T) is classified Pathogenic in FLT4 (ClinVar, No assertion criteria, 1 submitter). Very rare (popmax 8.47e-05%, nfe); Associated with congenital heart defects, multiple types, 7.

What condition is associated with FLT4 p.Arg82Ter (c.244C>T)?

FLT4 p.Arg82Ter (c.244C>T) is associated with congenital heart defects, multiple types, 7 (ClinVar).

How common is FLT4 p.Arg82Ter (c.244C>T) in the general population?

FLT4 p.Arg82Ter (c.244C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

FLT4 p.Arg82Ter

c.244C>T · rs2127839096 · VCV1177461

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

congenital heart defects, multiple types, 7

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 3 of 30
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.5	GERP -2.7, phastCons 0.99
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,948 alleles

Overall 6.2e-05% 1/1,612,376 alleles · very rare exomes 1/1,460,172 · genomes 0/152,204 · joint denominator

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: FLT4
Protein: p.Arg82Ter
Coding: c.244C>T
MANE Select: NM_182925
dbSNP: rs2127839096
Type: single nucleotide variant
Location: chr5:180630711 (GRCh38)
Gene constraint: LOEUF 0.265 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.82 · 2 PDB
Residue 82: the ig-like c2-type 1 domain; a UniProt-annotated variant site (in chtd7)

Full FLT4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital heart defects, multiple types, 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FLT4 p.Arg82Gln Likely benign ★★ same residue
FLT4 p.Arg318Ter Pathogenic/Likely pathogenic ★★ same condition
FLT4 p.Pro1137Leu Likely pathogenic ★★ same condition
FLT4 p.Arg1060Gln Uncertain significance ★★ ⚠ same condition
FLT4 p.Met1260Leu Uncertain significance ★★ ⚠ same condition
FLT4 p.Pro922Leu Uncertain significance ★★ ⚠ same condition
FLT4 c.1103+18C>T Benign/Likely benign ★★ same condition
FLT4 c.1103+20A>C Benign/Likely benign ★★ 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/flt4-p-arg82ter (accessed [today's date]).

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