Is VPS13D p.Gly2926Val (c.8777G>T) pathogenic?

VPS13D p.Gly2926Val (c.8777G>T) is classified Uncertain significance in VPS13D (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-31). AlphaMissense: likely benign (0.0827); Ultra-rare (popmax 0.015%, amr); Associated with Inborn genetic diseases.

What condition is associated with VPS13D p.Gly2926Val (c.8777G>T)?

VPS13D p.Gly2926Val (c.8777G>T) is associated with Inborn genetic diseases (ClinVar).

How common is VPS13D p.Gly2926Val (c.8777G>T) in the general population?

VPS13D p.Gly2926Val (c.8777G>T) is ultra-rare (popmax 0.015%, amr) (gnomAD).

What do computational predictors say about VPS13D p.Gly2926Val (c.8777G>T)?

AlphaMissense predicts likely benign (score 0.0827) — an in-silico prediction, not a clinical call.

VPS13D p.Gly2926Val

c.8777G>T · VCV3979954

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0827 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0827	likely benign
REVEL	0.206	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 4.4	GERP 0.28, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 181 kb · p 6.5e-14 · regional, not allelic
Overall
CADD	17.73	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 0.015% Admixed American · 9/60,002 alleles

Filtering AF 0.00773% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00579%

Overall 0.000558% 9/1,613,532 alleles · ultra-rare exomes 8/1,461,342 · genomes 1/152,190 · 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: VPS13D
Protein: p.Gly2926Val
Coding: c.8777G>T
MANE Select: NM_015378
Type: single nucleotide variant
Location: chr1:12342943 (GRCh38)
Gene constraint: LOEUF 0.426 · pLI 1.00 (gnomAD)
Residue 2926: a UniProt-annotated variant site (in scar4); a UniProt-annotated variant site (in scar4; altered mitochondrial morphology in patient cells); a UniProt-annotated variant site (in scar4; decreased protein abundance; altered mitochondrial morphology in patient cells)

Full VPS13D 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

VPS13D p.Arg3253Ter Pathogenic/Likely pathogenic ★★ same condition
VPS13D p.Ala1265Ser Uncertain significance ★★ ⚠ same condition
VPS13D p.Ala171Gly Uncertain significance ★★ same condition
VPS13D p.Ala2557Val Uncertain significance ★★ same condition
VPS13D p.Ala3621Val Uncertain significance ★★ ⚠ same condition
VPS13D p.Ala3685Ser Uncertain significance ★★ ⚠ same condition
VPS13D p.Arg1036Gln Uncertain significance ★★ ⚠ same condition
VPS13D p.Arg1036Trp 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/vps13d-p-gly2926val (accessed [today's date]).

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