Is VIP p.Ala128= (c.384A>C) pathogenic?

VIP p.Ala128= (c.384A>C) is classified Benign in VIP (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). Rare (popmax 0.657%, afr).

How common is VIP p.Ala128= (c.384A>C) in the general population?

VIP p.Ala128= (c.384A>C) is rare (popmax 0.657%, afr) (gnomAD).

VIP p.Ala128=

c.384A>C · rs35354531 · VCV776175

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.657%, 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.
REVEL	0.119	moderately benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -5.6	GERP -4.1
Overall
CADD	0.509	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.657% African / African-American · 492/74,892 alleles

Filtering AF 0.609% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.59%

Overall 0.036% 581/1,611,782 alleles · rare exomes 283/1,459,640 · genomes 298/152,142 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.657%	152
Admixed American	0.0852%	1,174
Remaining individualsnot grpmax-eligible	0.0545%	1,835
Middle Eastern	0.0165%	6,044
European (non-Finnish)	0.000255%	392,822

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: VIP
Protein: p.Ala128=
Coding: c.384A>C
MANE Select: NM_003381
dbSNP: rs35354531
Type: single nucleotide variant
Location: chr6:152756182 (GRCh38)

Full VIP 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/vip-p-ala128 (accessed [today's date]).

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