Is FLT4 p.Val511Ala (c.1532T>C) pathogenic?

FLT4 p.Val511Ala (c.1532T>C) is classified Uncertain significance in FLT4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-06). AlphaMissense: likely benign (0.23); Ultra-rare (popmax 0.0134%, afr); Associated with Inborn genetic diseases.

What condition is associated with FLT4 p.Val511Ala (c.1532T>C)?

FLT4 p.Val511Ala (c.1532T>C) is associated with Inborn genetic diseases (ClinVar).

How common is FLT4 p.Val511Ala (c.1532T>C) in the general population?

FLT4 p.Val511Ala (c.1532T>C) is ultra-rare (popmax 0.0134%, afr) (gnomAD).

What do computational predictors say about FLT4 p.Val511Ala (c.1532T>C)?

AlphaMissense predicts likely benign (score 0.23) — an in-silico prediction, not a clinical call.

FLT4 p.Val511Ala

c.1532T>C · VCV3516115

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.23 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.23	likely benign
REVEL	0.674	pathogenic-leaning
SaProt	LLR -1.09	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.3, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 15 kb · p 1.4e-05 · regional, not allelic
Overall
CADD	27.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% African / African-American · 10/74,850 alleles

Filtering AF 0.00724% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0055%

Overall 0.000744% 12/1,613,368 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0134%	7,485
Admixed American	0.00333%	29,997

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.Val511Ala
Coding: c.1532T>C
MANE Select: NM_182925
Type: single nucleotide variant
Location: chr5:180623951 (GRCh38)
Gene constraint: LOEUF 0.265 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.82 · 2 PDB
Residue 511: a β-strand; a disulfide bond; a UniProt-annotated variant site (in chtd7); the ig-like c2-type 5 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FLT4 p.Gly1131Ser Pathogenic/Likely pathogenic ★★ same condition
FLT4 p.Ala702Ser Uncertain significance ★★ ⚠ same condition
FLT4 p.Arg1189His Uncertain significance ★★ ⚠ same condition
FLT4 p.Glu207Lys Uncertain significance ★★ ⚠ same condition
FLT4 p.Glu365Lys Uncertain significance ★★ ⚠ same condition
FLT4 p.Gly4Ala Uncertain significance ★★ ⚠ same condition
FLT4 p.Met1260Leu Uncertain significance ★★ ⚠ same condition
FLT4 p.Pro922Leu 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-val511ala (accessed [today's date]).

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