Is VPS16 p.Ala6= (c.18G>A) pathogenic?

VPS16 p.Ala6= (c.18G>A) is classified Likely benign in VPS16 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-01). Ultra-rare (popmax 0.0575%, afr).

How common is VPS16 p.Ala6= (c.18G>A) in the general population?

VPS16 p.Ala6= (c.18G>A) is ultra-rare (popmax 0.0575%, afr) (gnomAD).

VPS16 p.Ala6=

c.18G>A · VCV4534731

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0575%, afr)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.37	GERP -5.4, phastCons 0.98
Overall
CADD	14.74	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0575% African / African-American · 42/73,060 alleles

Filtering AF 0.0437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0388%

Overall 0.00284% 44/1,548,398 alleles · ultra-rare exomes 21/1,396,064 · genomes 23/152,334 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0575%	1,740
Admixed American	0.00196%	50,994
South Asian	0.00119%	83,982

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: VPS16
Protein: p.Ala6=
Coding: c.18G>A
MANE Select: NM_022575
Type: single nucleotide variant
Location: chr20:2840792 (GRCh38)

Full VPS16 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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-ala6 (accessed [today's date]).

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