Is VPS53 p.Ser804= (c.2412C>T) pathogenic?

VPS53 p.Ser804= (c.2412C>T) is classified Likely benign in VPS53 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-11). Ultra-rare (popmax 0.0167%, mid).

How common is VPS53 p.Ser804= (c.2412C>T) in the general population?

VPS53 p.Ser804= (c.2412C>T) is ultra-rare (popmax 0.0167%, mid) (gnomAD).

VPS53 p.Ser804=

c.2412C>T · rs768263237 · VCV1207849

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, 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 0.5	GERP -1.1, phastCons 0.02
Overall
CADD	8.359	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0167% Middle Eastern · 1/6,000 alleles

Filtering AF 0.0118% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0111%

Overall 0.0121% 187/1,549,514 alleles · ultra-rare exomes 167/1,397,278 · genomes 20/152,236 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0301%	3,324
Middle Easterngrpmax	0.0167%	6,000
European (non-Finnish)	0.0136%	7,348
Remaining individualsnot grpmax-eligible	0.0133%	7,495
Ashkenazi Jewishnot grpmax-eligible	0.00351%	28,528
East Asian	0.00245%	40,842
South Asian	0.00239%	41,912

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: VPS53
Protein: p.Ser804=
Coding: c.2412C>T
MANE Select: NM_001128159
dbSNP: rs768263237
Type: single nucleotide variant
Location: chr17:519215 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.86
Residue 804: the 'disordered' region

Full VPS53 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

VPS53 c.1556+5G>A Pathogenic/Likely pathogenic ★★ same type
VPS53 p.Gln695Arg Pathogenic ★★ same type
VPS53 p.Ala222Thr Uncertain significance ★★ ⚠ same type
VPS53 p.Ala412Thr Uncertain significance ★★ ⚠ same type
VPS53 p.Arg140Cys Uncertain significance ★★ ⚠ same type
VPS53 p.Arg333Cys Uncertain significance ★★ ⚠ same type
VPS53 p.Asp462Asn Uncertain significance ★★ ⚠ same type
VPS53 p.Gly233Glu 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/vps53-p-ser804 (accessed [today's date]).

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