Is GAPVD1 p.Asp646= (c.1938C>T) pathogenic?

GAPVD1 p.Asp646= (c.1938C>T) is classified Likely benign in GAPVD1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-01-30). Rare (popmax 0.163%, nfe); Associated with GAPVD1-related disorder.

What condition is associated with GAPVD1 p.Asp646= (c.1938C>T)?

GAPVD1 p.Asp646= (c.1938C>T) is associated with GAPVD1-related disorder (ClinVar).

How common is GAPVD1 p.Asp646= (c.1938C>T) in the general population?

GAPVD1 p.Asp646= (c.1938C>T) is rare (popmax 0.163%, nfe) (gnomAD).

GAPVD1 p.Asp646=

c.1938C>T · rs149991575 · VCV3033851

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.163%, nfe)

Conditions

GAPVD1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.138	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.13	GERP -3.3, phastCons 0.97
Overall
CADD	7.325	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.163% European (non-Finnish) · 1,911/1,173,082 alleles

Filtering AF 0.157% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.154%

Overall 0.129% 2,076/1,606,502 alleles · rare exomes 1,968/1,454,200 · genomes 108/152,302 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.163%	614
Remaining individualsnot grpmax-eligible	0.149%	669
Admixed American	0.085%	1,177
Middle Eastern	0.033%	3,026
African / African-American	0.0227%	4,405
East Asian	0.00223%	44,830
South Asian	0.0011%	90,946

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.Asp646=
Coding: c.1938C>T
MANE Select: NM_001282680
dbSNP: rs149991575
Type: single nucleotide variant
Location: chr9:125326495 (GRCh38)
Gene constraint: LOEUF 0.34 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.17

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-asp646 (accessed [today's date]).

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