Is FLT4 p.Ser26Ala (c.76T>G) pathogenic?

FLT4 p.Ser26Ala (c.76T>G) is classified Benign in FLT4 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2023-09-01). AlphaMissense: likely benign (0.1413); Low-frequency (popmax 2.37%, afr).

How common is FLT4 p.Ser26Ala (c.76T>G) in the general population?

FLT4 p.Ser26Ala (c.76T>G) is low-frequency (popmax 2.37%, afr) (gnomAD).

What do computational predictors say about FLT4 p.Ser26Ala (c.76T>G)?

AlphaMissense predicts likely benign (score 0.1413) — an in-silico prediction, not a clinical call.

FLT4 p.Ser26Ala

c.76T>G · rs113995355 · VCV702770

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1413 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.37%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1413	likely benign
REVEL	0.126	moderately benign-leaning
SaProt	LLR -6.75	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.1, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 19 kb · p 0.1 · regional, not allelic
Overall
CADD	23.9	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 2.37% African / African-American · 1,778/75,000 alleles

Filtering AF 2.28% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.24%

Overall 0.12% 1,935/1,609,666 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.37%	42
Remaining individualsnot grpmax-eligible	0.139%	717
Admixed American	0.09%	1,111
Middle Eastern	0.0826%	1,211
South Asian	0.00439%	22,768
European (non-Finnish)	0.000593%	168,526

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.Ser26Ala
Coding: c.76T>G
MANE Select: NM_182925
dbSNP: rs113995355
Type: single nucleotide variant
Location: chr5:180631761 (GRCh38)
Gene constraint: LOEUF 0.265 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.82 · 2 PDB

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

Similar variants

FLT4 p.Ser26Phe Uncertain significance ⚠ same residue
FLT4 p.Arg1041Gln Pathogenic/Likely pathogenic ★★ same type
FLT4 p.Arg1041Trp Pathogenic/Likely pathogenic ★★ same type
FLT4 p.Arg318Ter Pathogenic/Likely pathogenic ★★ same type
FLT4 p.Gly1131Ser Pathogenic/Likely pathogenic ★★ same type
FLT4 p.Gly857Arg Pathogenic ★★ same type
FLT4 p.Pro1137Leu Likely pathogenic ★★ same type
FLT4 p.Ala702Ser Uncertain significance ★★ ⚠ same type

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-ser26ala (accessed [today's date]).

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