Is VPS13A p.Ser751Phe (c.2252C>T) pathogenic?

VPS13A p.Ser751Phe (c.2252C>T) is classified Uncertain significance in VPS13A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-29). AlphaMissense: likely benign (0.2576); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with VPS13A p.Ser751Phe (c.2252C>T)?

VPS13A p.Ser751Phe (c.2252C>T) is associated with Inborn genetic diseases (ClinVar).

How common is VPS13A p.Ser751Phe (c.2252C>T) in the general population?

VPS13A p.Ser751Phe (c.2252C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about VPS13A p.Ser751Phe (c.2252C>T)?

AlphaMissense predicts likely benign (score 0.2576) — an in-silico prediction, not a clinical call.

VPS13A p.Ser751Phe

c.2252C>T · VCV3332161

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2576 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2576	likely benign
REVEL	0.229	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 176 kb · p 0.00021 · regional, not allelic
Overall
CADD	26.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: VPS13A
Protein: p.Ser751Phe
Coding: c.2252C>T
MANE Select: NM_033305
Type: single nucleotide variant
Location: chr9:77252316 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

VPS13A p.Ser751= Likely benign ★ same residue
VPS13A p.Arg1297Ter Pathogenic/Likely pathogenic ★★ same condition
VPS13A p.Ala1193Val Uncertain significance ★★ same condition
VPS13A p.Ala1518Glu Uncertain significance ★★ ⚠ same condition
VPS13A p.Ala405Thr Uncertain significance ★★ same condition
VPS13A p.Arg1098Lys Uncertain significance ★★ ⚠ same condition
VPS13A p.Arg1386His Uncertain significance ★★ ⚠ same condition
VPS13A p.Arg169Trp Uncertain significance ★★ ⚠ same condition

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-ser751phe (accessed [today's date]).

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