Is GAPVD1 p.Ser1384= (c.4152T>G) pathogenic?

GAPVD1 p.Ser1384= (c.4152T>G) is classified Likely benign in GAPVD1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-24). Rare (popmax 0.264%, mid); Associated with GAPVD1-related disorder.

What condition is associated with GAPVD1 p.Ser1384= (c.4152T>G)?

GAPVD1 p.Ser1384= (c.4152T>G) is associated with GAPVD1-related disorder (ClinVar).

How common is GAPVD1 p.Ser1384= (c.4152T>G) in the general population?

GAPVD1 p.Ser1384= (c.4152T>G) is rare (popmax 0.264%, mid) (gnomAD).

GAPVD1 p.Ser1384=

c.4152T>G · rs866131895 · VCV3050782

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.264%, mid)

Conditions

GAPVD1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.52	GERP -1.2, phastCons 1
Overall
CADD	9.356	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.264% Middle Eastern · 16/6,060 alleles

Filtering AF 0.166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.135%

Overall 0.000991% 16/1,614,004 alleles · rare exomes 16/1,461,698 · genomes 0/152,306 · 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: GAPVD1
Protein: p.Ser1384=
Coding: c.4152T>G
MANE Select: NM_001282680
dbSNP: rs866131895
Type: single nucleotide variant
Location: chr9:125360635 (GRCh38)
Gene constraint: LOEUF 0.34 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.17
Residue 1384: the vps9 domain

Full GAPVD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

GAPVD1-related disorder

Similar variants

GAPVD1 p.Arg1306Trp Uncertain significance ★ ⚠ same condition
GAPVD1 p.Arg487His Uncertain significance ★ ⚠ same condition
GAPVD1 p.Arg564His Uncertain significance ★ ⚠ same condition
GAPVD1 p.Ile1456Val Uncertain significance ★ ⚠ same condition
GAPVD1 p.Ser112Phe Uncertain significance ⚠ same condition
GAPVD1 c.1251+7G>A Likely benign same condition
GAPVD1 c.1441+17G>T Likely benign same condition
GAPVD1 c.1442-8T>C Likely benign 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/gapvd1-p-ser1384 (accessed [today's date]).

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