Is VIM c.1008+1G>A pathogenic?

VIM c.1008+1G>A is classified Uncertain significance in VIM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-13). Very rare (popmax 0.00167%, amr); Associated with cataract 30.

What condition is associated with VIM c.1008+1G>A?

VIM c.1008+1G>A is associated with cataract 30 (ClinVar).

How common is VIM c.1008+1G>A in the general population?

VIM c.1008+1G>A is very rare (popmax 0.00167%, amr) (gnomAD).

VIM c.1008+1G>A

VCV4279621

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

cataract 30

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	canonical splice-site (±1/±2)	predicted loss-of-function
REVEL	0.388	indeterminate
Splicing
Splice region	donor +1	canonical splice dinucleotide (donor +1) · inside the BP7-excluded zone
SpliceAI	Δ1.00	donor loss · deltas
Pangolin	Δ0.87	loss · gain 0.32 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Non-coding constraint	Z 1.46	1 kb window · o/e 0.90 · regional · uncalibrated
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,998 alleles

Overall 0.000186% 3/1,613,950 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,998
South Asian	0.0011%	91,086
European (non-Finnish)	8.47e-05%	1,180,012

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+1G>A
MANE Select: NM_003380
Type: single nucleotide variant
Location: chr10:17234819 (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.1008+18A>G Benign/Likely benign ★★ same condition
VIM c.1009-10C>T Benign ★★ same condition
VIM c.1360-18G>T 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-1g-a (accessed [today's date]).

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