Is FLT4 p.Thr323= (c.969C>T) pathogenic?

FLT4 p.Thr323= (c.969C>T) is classified Likely benign in FLT4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-11-16). Very rare (popmax 0.00667%, afr); Associated with FLT4-related disorder.

What condition is associated with FLT4 p.Thr323= (c.969C>T)?

FLT4 p.Thr323= (c.969C>T) is associated with FLT4-related disorder (ClinVar).

How common is FLT4 p.Thr323= (c.969C>T) in the general population?

FLT4 p.Thr323= (c.969C>T) is very rare (popmax 0.00667%, afr) (gnomAD).

FLT4 p.Thr323=

c.969C>T · rs371544933 · VCV3031287

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00667%, afr)

Conditions

FLT4-related disorder

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 -5.6	GERP -2.7
Overall
CADD	7.769	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% African / African-American · 5/74,940 alleles

Filtering AF 0.0041% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00372%

Overall 0.00422% 68/1,612,976 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00667%	14,988
European (non-Finnish)	0.00517%	19,344
Admixed American	0.00167%	60,010
Remaining individualsnot grpmax-eligible	0.0016%	62,460

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.Thr323=
Coding: c.969C>T
MANE Select: NM_182925
dbSNP: rs371544933
Type: single nucleotide variant
Location: chr5:180629275 (GRCh38)
Gene constraint: LOEUF 0.265 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.82 · 2 PDB
Residue 323: a UniProt-annotated variant site (in chtd7); the ig-like c2-type 3 domain

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

Disease context

FLT4-related disorder

Similar variants

FLT4 p.Thr323Ala Uncertain significance ★ ⚠ same residue
FLT4 p.Gly857Arg Pathogenic ★★ same condition
FLT4 p.Pro1137Leu Likely pathogenic ★★ same condition
FLT4 p.Ser393Arg Uncertain significance ★★ ⚠ same condition
FLT4 c.2168-1G>A Likely pathogenic ★ same condition
FLT4 p.Arg1041Gly Likely pathogenic ★ same condition
FLT4 p.Gln1020Leu Pathogenic ★ same condition
FLT4 p.Gln1179Ter Pathogenic ★ 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-thr323 (accessed [today's date]).

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