Is GAPVD1 p.Thr751= (c.2253G>A) pathogenic?

GAPVD1 p.Thr751= (c.2253G>A) is classified Likely benign in GAPVD1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-05-05). Rare (popmax 0.535%, amr); Associated with GAPVD1-related disorder.

What condition is associated with GAPVD1 p.Thr751= (c.2253G>A)?

GAPVD1 p.Thr751= (c.2253G>A) is associated with GAPVD1-related disorder (ClinVar).

How common is GAPVD1 p.Thr751= (c.2253G>A) in the general population?

GAPVD1 p.Thr751= (c.2253G>A) is rare (popmax 0.535%, amr) (gnomAD).

GAPVD1 p.Thr751=

c.2253G>A · rs183996407 · VCV3057525

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.535%, amr)

Conditions

GAPVD1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.033	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.5	GERP -5.6
Overall
CADD	7.614	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.535% Admixed American · 321/60,018 alleles

Filtering AF 0.487% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.468%

Overall 0.0212% 342/1,612,856 alleles · rare exomes 186/1,460,590 · genomes 156/152,266 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.535%	187
Remaining individualsnot grpmax-eligible	0.0192%	5,206
South Asian	0.0033%	30,349
African / African-American	0.00133%	75,018
European (non-Finnish)	0.000424%	235,768

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.Thr751=
Coding: c.2253G>A
MANE Select: NM_001282680
dbSNP: rs183996407
Type: single nucleotide variant
Location: chr9:125332005 (GRCh38)
Gene constraint: LOEUF 0.34 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.17
Residue 751: the 'disordered' region

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-thr751 (accessed [today's date]).

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