Is FLT4 p.Ser1275= (c.3825T>C) pathogenic?

FLT4 p.Ser1275= (c.3825T>C) is classified Likely benign in FLT4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-08-15). Ultra-rare (popmax 0.0165%, mid); Associated with FLT4-related disorder.

What condition is associated with FLT4 p.Ser1275= (c.3825T>C)?

FLT4 p.Ser1275= (c.3825T>C) is associated with FLT4-related disorder (ClinVar).

How common is FLT4 p.Ser1275= (c.3825T>C) in the general population?

FLT4 p.Ser1275= (c.3825T>C) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

FLT4 p.Ser1275=

c.3825T>C · rs1407525547 · VCV3043868

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

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 0.57	GERP -1.3, phastCons 0.91
Overall
CADD	7.052	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000684% 10/1,461,852 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0032%	31,256
European (non-Finnish)	0.000593%	168,568

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.Ser1275=
Coding: c.3825T>C
MANE Select: NM_182925
dbSNP: rs1407525547
Type: single nucleotide variant
Location: chr5:180609036 (GRCh38)
Gene constraint: LOEUF 0.265 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.82 · 2 PDB
Residue 1275: a UniProt-annotated variant site (in chtd7)

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

Disease context

FLT4-related disorder

Similar variants

FLT4 p.Ser1275Ile Uncertain significance ★ same residue
FLT4 p.Ser1275Asn Uncertain significance ★★ ⚠ same residue
FLT4 p.Ser1275Gly Likely pathogenic ★ same residue
FLT4 p.Ser1275Cys Uncertain significance ★ same residue
FLT4 p.Ser1275Thr Uncertain significance ★ ⚠ same residue
FLT4 p.Gly857Arg Pathogenic ★★ same condition
FLT4 p.Pro1137Leu Likely pathogenic ★★ same condition
FLT4 p.Ser393Arg 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/flt4-p-ser1275 (accessed [today's date]).

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