Is VPS13D p.Pro607= (c.1821C>T) pathogenic?

VPS13D p.Pro607= (c.1821C>T) is classified Likely benign in VPS13D (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-08). Very rare (popmax 0.00712%, nfe); Associated with Inborn genetic diseases.

What condition is associated with VPS13D p.Pro607= (c.1821C>T)?

VPS13D p.Pro607= (c.1821C>T) is associated with Inborn genetic diseases (ClinVar).

How common is VPS13D p.Pro607= (c.1821C>T) in the general population?

VPS13D p.Pro607= (c.1821C>T) is very rare (popmax 0.00712%, nfe) (gnomAD).

VPS13D p.Pro607=

c.1821C>T · rs144149396 · VCV2075121

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00712%, nfe)

Conditions

Inborn genetic diseases

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 -8.2	GERP -3.5
Overall
CADD	0.263	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00712% European (non-Finnish) · 84/1,179,800 alleles

Filtering AF 0.00588% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00541%

Overall 0.00886% 143/1,613,306 alleles · very rare exomes 134/1,461,214 · genomes 9/152,092 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0766%	1,306
European (non-Finnish)grpmax	0.00712%	14,045
Remaining individualsnot grpmax-eligible	0.0064%	15,617
South Asian	0.0044%	22,729
East Asian	0.00223%	44,884
Admixed American	0.00167%	59,834

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro607=
Coding: c.1821C>T
MANE Select: NM_015378
dbSNP: rs144149396
Type: single nucleotide variant
Location: chr1:12268725 (GRCh38)
Gene constraint: LOEUF 0.426 · pLI 1.00 (gnomAD)

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-pro607 (accessed [today's date]).

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