Is VIM c.1008+18A>G pathogenic?

VIM c.1008+18A>G is classified Benign/Likely benign in VIM (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-10-23). Low-frequency (popmax 1.47%, mid); Associated with cataract 30.

What condition is associated with VIM c.1008+18A>G?

VIM c.1008+18A>G is associated with cataract 30 (ClinVar).

How common is VIM c.1008+18A>G in the general population?

VIM c.1008+18A>G is low-frequency (popmax 1.47%, mid) (gnomAD).

VIM c.1008+18A>G

rs368836644 · VCV1600245

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.47%, mid)

Conditions

cataract 30

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +18	near-intronic (+18 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.039	GERP -3.4
Non-coding constraint	Z 1.46	1 kb window · o/e 0.90 · regional · uncalibrated
Overall
CADD	1.467	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.47% Middle Eastern · 89/6,062 alleles

Filtering AF 1.22% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.13%

Overall 0.107% 1,722/1,614,134 alleles · low-frequency exomes 1,556/1,461,812 · genomes 166/152,322 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	1.47%	68
South Asian	0.375%	266
Remaining individualsnot grpmax-eligible	0.202%	496
Admixed American	0.162%	619
African / African-American	0.0879%	1,137
European (non-Finnish)	0.0827%	1,209
Ashkenazi Jewishnot grpmax-eligible	0.0507%	1,974
Finnishnot grpmax-eligible	0.0172%	5,818

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: VIM
Coding: c.1008+18A>G
MANE Select: NM_003380
dbSNP: rs368836644
Type: single nucleotide variant
Location: chr10:17234836 (GRCh38)
Gene constraint: LOEUF 0.542 · pLI 0.86 (gnomAD)
Structure: AlphaFold pLDDT 78.05 · 26 PDB

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

Disease context

cataract 30 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

VIM p.Arg45His Uncertain significance ★★ ⚠ same condition
VIM p.Asp360Glu Uncertain significance ★★ ⚠ same condition
VIM p.Leu164Val Uncertain significance ★★ ⚠ same condition
VIM p.Thr458Ala Uncertain significance ★★ ⚠ same condition
VIM p.Val272Ile Uncertain significance ★★ ⚠ same condition
VIM c.1009-10C>T Benign ★★ same condition
VIM c.1360-18G>T Likely benign ★★ same condition
VIM c.720+18C>T Benign/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/vim-c-1008-plus-18a-g (accessed [today's date]).

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