Is VPS51 p.Arg232= (c.696C>G) pathogenic?

VPS51 p.Arg232= (c.696C>G) is classified Likely benign in VPS51 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-01). Ultra-rare (popmax 0.0382%, mid).

How common is VPS51 p.Arg232= (c.696C>G) in the general population?

VPS51 p.Arg232= (c.696C>G) is ultra-rare (popmax 0.0382%, mid) (gnomAD).

VPS51 p.Arg232=

c.696C>G · rs377335542 · VCV2641945

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0382%, mid)

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 -0.77	GERP -3.7, phastCons 0.003
Overall
CADD	2.852	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0382% Middle Eastern · 2/5,234 alleles

Filtering AF 0.0125% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0118%

Overall 0.0112% 174/1,549,318 alleles · ultra-rare exomes 166/1,397,084 · genomes 8/152,234 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0382%	2,617
European (non-Finnish)	0.0143%	7,006
Remaining individualsnot grpmax-eligible	0.00834%	11,984
African / African-American	0.00409%	24,455

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: VPS51
Protein: p.Arg232=
Coding: c.696C>G
MANE Select: NM_013265
dbSNP: rs377335542
Type: single nucleotide variant
Location: chr11:65107993 (GRCh38)
Gene constraint: LOEUF 1.284 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.07 · 1 PDB

Full VPS51 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

VPS51 p.Arg232Cys Uncertain significance ★ ⚠ same residue
VPS51 p.Arg232Leu Uncertain significance ★ ⚠ same residue
VPS51 p.Ala357Val Uncertain significance ★★ ⚠ same type
VPS51 p.Arg240His Uncertain significance ★★ ⚠ same type
VPS51 p.Pro11Leu Uncertain significance ★★ ⚠ same type
VPS51 c.1443+4C>T Benign/Likely benign ★★ same type
VPS51 c.1444-12C>T Benign ★★ same type
VPS51 c.1879-7C>T Benign ★★ 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/vps51-p-arg232 (accessed [today's date]).

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