Is VAV1 p.Phe100= (c.300C>T) pathogenic?

VAV1 p.Phe100= (c.300C>T) is classified Likely benign in VAV1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-31). Ultra-rare (popmax 0.0117%, amr).

How common is VAV1 p.Phe100= (c.300C>T) in the general population?

VAV1 p.Phe100= (c.300C>T) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

VAV1 p.Phe100=

c.300C>T · rs147883329 · VCV1565424

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5	GERP -3.6
Overall
CADD	5.98	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0117% Admixed American · 7/59,996 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.0044% 71/1,614,064 alleles · ultra-rare exomes 62/1,461,868 · genomes 9/152,196 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,571
African / African-American	0.0107%	9,365
European (non-Finnish)	0.00458%	21,853
East Asian	0.00223%	44,894
Remaining individualsnot grpmax-eligible	0.0016%	62,490

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: VAV1
Protein: p.Phe100=
Coding: c.300C>T
MANE Select: NM_005428
dbSNP: rs147883329
Type: single nucleotide variant
Location: chr19:6820797 (GRCh38)
Gene constraint: LOEUF 0.353 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.63 · 10 PDB
Residue 100: the calponin-homology (ch) domain; an α-helix

Full VAV1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

VAV1 p.Ala168Val Uncertain significance ★★ ⚠ same type
VAV1 p.Ala362Thr Uncertain significance ★★ ⚠ same type
VAV1 p.Ala734Thr Uncertain significance ★★ same type
VAV1 p.Arg15Gln Uncertain significance ★★ ⚠ same type
VAV1 p.Arg179Ser Uncertain significance ★★ ⚠ same type
VAV1 p.Arg195His Uncertain significance ★★ ⚠ same type
VAV1 p.Arg282His Uncertain significance ★★ ⚠ same type
VAV1 p.Arg296His 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/vav1-p-phe100 (accessed [today's date]).

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