Is VPS13A p.Ala487Gly (c.1460C>G) pathogenic?

VPS13A p.Ala487Gly (c.1460C>G) is classified Likely benign in VPS13A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-16). AlphaMissense: likely benign (0.1145); Ultra-rare (popmax 0.027%, amr); Associated with Inborn genetic diseases.

What condition is associated with VPS13A p.Ala487Gly (c.1460C>G)?

VPS13A p.Ala487Gly (c.1460C>G) is associated with Inborn genetic diseases (ClinVar).

How common is VPS13A p.Ala487Gly (c.1460C>G) in the general population?

VPS13A p.Ala487Gly (c.1460C>G) is ultra-rare (popmax 0.027%, amr) (gnomAD).

What do computational predictors say about VPS13A p.Ala487Gly (c.1460C>G)?

AlphaMissense predicts likely benign (score 0.1145) — an in-silico prediction, not a clinical call.

VPS13A p.Ala487Gly

c.1460C>G · VCV3468205

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1145 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.027%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1145	likely benign
REVEL	0.109	moderately 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 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 176 kb · p 0.00021 · regional, not allelic
Overall
CADD	21.4	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.027% Admixed American · 16/59,318 alleles

Filtering AF 0.0169% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0138%

Overall 0.001% 16/1,597,732 alleles · ultra-rare exomes 14/1,445,980 · genomes 2/151,752 · 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.Ala487Gly
Coding: c.1460C>G
MANE Select: NM_033305
Type: single nucleotide variant
Location: chr9:77228129 (GRCh38)
Gene constraint: LOEUF 0.696 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 487: 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.Ala487Asp Uncertain significance ⚠ 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-ala487gly (accessed [today's date]).

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