Is VEGFC p.Pro154Ser (c.460C>T) pathogenic?

VEGFC p.Pro154Ser (c.460C>T) is classified Uncertain significance in VEGFC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-25). AlphaMissense: likely pathogenic (0.9965); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with VEGFC p.Pro154Ser (c.460C>T)?

VEGFC p.Pro154Ser (c.460C>T) is associated with Inborn genetic diseases (ClinVar).

How common is VEGFC p.Pro154Ser (c.460C>T) in the general population?

VEGFC p.Pro154Ser (c.460C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about VEGFC p.Pro154Ser (c.460C>T)?

AlphaMissense predicts likely pathogenic (score 0.9965) — an in-silico prediction, not a clinical call.

VEGFC p.Pro154Ser

c.460C>T · VCV3814887

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9965 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9965	likely pathogenic · top 2% in VEGFC
REVEL	0.826	moderately pathogenic-leaning
SaProt	LLR -13.09	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 108 kb · p 0.072 · regional, not allelic
Overall
CADD	29.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: VEGFC
Protein: p.Pro154Ser
Coding: c.460C>T
MANE Select: NM_005429
Type: single nucleotide variant
Location: chr4:176727870 (GRCh38)
Gene constraint: LOEUF 0.379 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.67 · 4 PDB
Residue 154: a β-strand

Full VEGFC 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

VEGFC p.Ala112Thr Uncertain significance ★ ⚠ same condition
VEGFC p.Ala16Asp Uncertain significance ★ ⚠ same condition
VEGFC p.Ala28Val Uncertain significance ★ ⚠ same condition
VEGFC p.Ala41Pro Uncertain significance ★ ⚠ same condition
VEGFC p.Ala48Gly Uncertain significance ★ ⚠ same condition
VEGFC p.Arg134Trp Uncertain significance ★ ⚠ same condition
VEGFC p.Arg161Ser Uncertain significance ★ ⚠ same condition
VEGFC p.Asp216Gly 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/vegfc-p-pro154ser (accessed [today's date]).

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