Is VPS16 p.Phe413Val (c.1237T>G) pathogenic?

VPS16 p.Phe413Val (c.1237T>G) is classified Uncertain significance in VPS16 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-05). AlphaMissense: ambiguous (0.3578); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with VPS16 p.Phe413Val (c.1237T>G)?

VPS16 p.Phe413Val (c.1237T>G) is associated with Inborn genetic diseases (ClinVar).

How common is VPS16 p.Phe413Val (c.1237T>G) in the general population?

VPS16 p.Phe413Val (c.1237T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about VPS16 p.Phe413Val (c.1237T>G)?

AlphaMissense predicts ambiguous (score 0.3578) — an in-silico prediction, not a clinical call.

VPS16 p.Phe413Val

c.1237T>G · VCV4199156

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3578 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3578	ambiguous
REVEL	0.132	moderately benign-leaning
SaProt	LLR -11.30	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 26 kb · p 8.4e-07 · regional, not allelic
Overall
CADD	23.9	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

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: VPS16
Protein: p.Phe413Val
Coding: c.1237T>G
MANE Select: NM_022575
Type: single nucleotide variant
Location: chr20:2862840 (GRCh38)
Gene constraint: LOEUF 0.813 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.35 · 1 PDB
Residue 413: a UniProt-annotated variant site (in dyt30)

Full VPS16 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

VPS16 p.Arg129Gln Uncertain significance ★★ ⚠ same condition
VPS16 p.Arg262Trp Uncertain significance ★★ ⚠ same condition
VPS16 p.Arg273Cys Uncertain significance ★★ ⚠ same condition
VPS16 p.Arg317Cys Uncertain significance ★★ ⚠ same condition
VPS16 p.Glu297Lys Uncertain significance ★★ ⚠ same condition
VPS16 p.Glu96Lys Uncertain significance ★★ ⚠ same condition
VPS16 p.Leu66Val Uncertain significance ★★ ⚠ same condition
VPS16 p.Ser398Arg 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/vps16-p-phe413val (accessed [today's date]).

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