Is FLT4 p.Pro954Ser (c.2860C>T) pathogenic?

FLT4 p.Pro954Ser (c.2860C>T) is classified Benign/Likely benign in FLT4 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-01). AlphaMissense: likely benign (0.0879); Rare (popmax 0.694%, nfe); Associated with colorectal cancer.

What condition is associated with FLT4 p.Pro954Ser (c.2860C>T)?

FLT4 p.Pro954Ser (c.2860C>T) is associated with colorectal cancer, capillary infantile hemangioma (ClinVar).

How common is FLT4 p.Pro954Ser (c.2860C>T) in the general population?

FLT4 p.Pro954Ser (c.2860C>T) is rare (popmax 0.694%, nfe) (gnomAD).

What do computational predictors say about FLT4 p.Pro954Ser (c.2860C>T)?

AlphaMissense predicts likely benign (score 0.0879) — an in-silico prediction, not a clinical call.

FLT4 p.Pro954Ser

c.2860C>T · rs34255532 · VCV16264

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.0879 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.694%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

colorectal cancer

Computational evidence

Protein change
AlphaMissense	0.0879	likely benign
REVEL	0.157	moderately benign-leaning
SaProt	LLR -7.22	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 8.2	GERP 1.6, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 15 kb · p 1.4e-05 · regional, not allelic
Overall
CADD	22.1	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 0.694% European (non-Finnish) · 8,100/1,167,046 alleles

Filtering AF 0.681% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.676%

Overall 0.57% 9,046/1,585,876 alleles · rare exomes 8,519/1,433,578 · genomes 527/152,298 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.694%	144
Remaining individualsnot grpmax-eligible	0.61%	164
Middle Eastern	0.502%	199
South Asian	0.361%	277
Admixed American	0.18%	557
African / African-American	0.116%	859
Finnishnot grpmax-eligible	0.0586%	1,705
Ashkenazi Jewishnot grpmax-eligible	0.0138%	7,249

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.Pro954Ser
Coding: c.2860C>T
MANE Select: NM_182925
dbSNP: rs34255532
Type: single nucleotide variant
Location: chr5:180618911 (GRCh38)
Gene constraint: LOEUF 0.265 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.82 · 2 PDB
Residue 954: the protein kinase domain; a UniProt-annotated variant site (in chtd7); a UniProt-annotated variant site (in hci)

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

Disease context

colorectal cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: capillary infantile hemangioma

Similar variants

FLT4 p.Pro1137Leu Likely pathogenic ★★ same condition
FLT4 p.Arg1060Gln Uncertain significance ★★ ⚠ same condition
FLT4 p.Met1260Leu Uncertain significance ★★ ⚠ same condition
FLT4 p.Ala67Val Uncertain significance ★ ⚠ same condition
FLT4 p.Gly1238Arg Uncertain significance ★ ⚠ same condition
FLT4 p.Lys370Arg Uncertain significance ★ ⚠ same condition
FLT4 p.Arg1041Gln Pathogenic/Likely pathogenic ★★ same type
FLT4 p.Arg1041Trp Pathogenic/Likely pathogenic ★★ 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-pro954ser (accessed [today's date]).

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