Is VPS13A p.Ser751fs (c.2250_2253del) pathogenic?

VPS13A p.Ser751fs (c.22502253del) is classified Pathogenic in VPS13A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-14). Very rare (popmax 8.48e-05%, nfe).

How common is VPS13A p.Ser751fs (c.2250_2253del) in the general population?

VPS13A p.Ser751fs (c.2250_2253del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

VPS13A p.Ser751fs

c.2250_2253del · rs1825188053 · VCV2795769

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 22 of 72
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.1	GERP -4, phastCons 0.86

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,914 alleles

Overall 6.2e-05% 1/1,613,964 alleles · very rare exomes 1/1,461,732 · genomes 0/152,232 · joint denominator

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: VPS13A
Protein: p.Ser751fs
Coding: c.2250_2253del
MANE Select: NM_033305
dbSNP: rs1825188053
Type: Deletion
Location: chr9:77252312 (GRCh38)
Gene constraint: LOEUF 0.696 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 751: a UniProt-annotated variant site (in chac)

Full VPS13A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

VPS13A p.Ser751Phe Uncertain significance ★ ⚠ same residue
VPS13A p.Ser751= Likely benign ★ same residue
VPS13A c.7157_7172del Pathogenic/Likely pathogenic ★★ same type
VPS13A c.883-1_892del Likely pathogenic ★★ same type
VPS13A p.Ala332fs Pathogenic/Likely pathogenic ★★ same type
VPS13A p.Asn73fs Pathogenic/Likely pathogenic ★★ same type
VPS13A p.Gly3023fs Pathogenic/Likely pathogenic ★★ same type
VPS13A p.Ile1152fs Pathogenic/Likely pathogenic ★★ 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/vps13a-p-ser751fs (accessed [today's date]).

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