Is VEGFA p.Pro160Arg (c.479C>G) pathogenic?

VEGFA p.Pro160Arg (c.479C>G) is classified Uncertain significance in VEGFA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). Ultra-rare (popmax 0.0124%, afr).

How common is VEGFA p.Pro160Arg (c.479C>G) in the general population?

VEGFA p.Pro160Arg (c.479C>G) is ultra-rare (popmax 0.0124%, afr) (gnomAD).

VEGFA p.Pro160Arg

c.479C>G · VCV4198630

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0124%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.089	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.7	GERP 1.5, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 6,764 bp · p 0.31 · regional, not allelic
Overall
CADD	20.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0124% African / African-American · 9/72,820 alleles

Filtering AF 0.0064% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00479%

Overall 0.000691% 11/1,592,912 alleles · ultra-rare exomes 8/1,440,988 · genomes 3/151,924 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0124%	8,091
Remaining individualsnot grpmax-eligible	0.00324%	30,835

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.Pro160Arg
Coding: c.479C>G
MANE Select: NM_003376
Type: single nucleotide variant
Location: chr6:43771185 (GRCh38)
Gene constraint: LOEUF 0.61 · pLI 0.19 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 65.32 · 57 PDB
Residue 160: the 'disordered' region

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-pro160arg (accessed [today's date]).

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