Is VPS13A p.Val1908Ile (c.5722G>A) pathogenic?

VPS13A p.Val1908Ile (c.5722G>A) is classified Uncertain significance in VPS13A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-23). AlphaMissense: likely benign (0.062); Very rare (popmax 0.00017%, nfe); Associated with Inborn genetic diseases.

What condition is associated with VPS13A p.Val1908Ile (c.5722G>A)?

VPS13A p.Val1908Ile (c.5722G>A) is associated with Inborn genetic diseases (ClinVar).

How common is VPS13A p.Val1908Ile (c.5722G>A) in the general population?

VPS13A p.Val1908Ile (c.5722G>A) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about VPS13A p.Val1908Ile (c.5722G>A)?

AlphaMissense predicts likely benign (score 0.062) — an in-silico prediction, not a clinical call.

VPS13A p.Val1908Ile

c.5722G>A · VCV3979928

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.062 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.062	likely benign
REVEL	0.014	strongly 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 -0.044	GERP -5.5
Regional constraint	o/e 0.93	unconstrained · MANE · 176 kb · p 0.00021 · regional, not allelic
Overall
CADD	0.15	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

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,556 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,334 alleles · very rare exomes 2/1,461,206 · genomes 0/152,128 · 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.Val1908Ile
Coding: c.5722G>A
MANE Select: NM_033305
Type: single nucleotide variant
Location: chr9:77321638 (GRCh38)
Gene constraint: LOEUF 0.696 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 1908: 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.Val1908= 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-val1908ile (accessed [today's date]).

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