Is VEGFA p.Phe64Ser (c.191T>C) pathogenic?

VEGFA p.Phe64Ser (c.191T>C) is classified Likely benign in VEGFA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-07). Very rare (popmax 8.73e-05%, nfe).

How common is VEGFA p.Phe64Ser (c.191T>C) in the general population?

VEGFA p.Phe64Ser (c.191T>C) is very rare (popmax 8.73e-05%, nfe) (gnomAD).

VEGFA p.Phe64Ser

c.191T>C · rs1282837263 · VCV2569575

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.73e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.029	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.12	GERP -0.7, phastCons 0.39
Regional constraint	o/e 1.06	unconstrained · MANE · 6,764 bp · p 0.31 · regional, not allelic
Overall
CADD	12.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.73e-05% European (non-Finnish) · 1/1,145,426 alleles

Overall 6.47e-05% 1/1,544,542 alleles · very rare exomes 1/1,392,564 · genomes 0/151,978 · joint denominator

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: VEGFA
Protein: p.Phe64Ser
Coding: c.191T>C
MANE Select: NM_003376
dbSNP: rs1282837263
Type: single nucleotide variant
Location: chr6:43770897 (GRCh38)
Gene constraint: LOEUF 0.61 · pLI 0.19 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 65.32 · 57 PDB

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

Similar variants

VEGFA p.Asn371= Likely benign ★★ same type
VEGFA c.1034+36G>C Uncertain significance ★ ⚠ same type
VEGFA c.1034+42C>T Uncertain significance ★ ⚠ same type
VEGFA p.Ala123Glu Uncertain significance ★ same type
VEGFA p.Ala133Glu Uncertain significance ★ same type
VEGFA p.Ala79Asp Uncertain significance ★ same type
VEGFA p.Arg114Pro Uncertain significance ★ same type
VEGFA p.Arg171Gly 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/vegfa-p-phe64ser (accessed [today's date]).

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