Is VIM p.Leu269= (c.807G>T) pathogenic?

VIM p.Leu269= (c.807G>T) is classified Benign in VIM (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-13). Rare (popmax 0.263%, amr); Associated with cataract 30.

What condition is associated with VIM p.Leu269= (c.807G>T)?

VIM p.Leu269= (c.807G>T) is associated with cataract 30 (ClinVar).

How common is VIM p.Leu269= (c.807G>T) in the general population?

VIM p.Leu269= (c.807G>T) is rare (popmax 0.263%, amr) (gnomAD).

VIM p.Leu269=

c.807G>T · rs745874397 · VCV1165657

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.263%, amr)

Conditions

cataract 30

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 6.7	GERP 1.1, phastCons 1
Overall
CADD	20.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.263% Admixed American · 158/60,006 alleles

Filtering AF 0.23% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.217%

Overall 0.0101% 163/1,614,032 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.263%	380
Remaining individualsnot grpmax-eligible	0.008%	12,498

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
Protein: p.Leu269=
Coding: c.807G>T
MANE Select: NM_003380
dbSNP: rs745874397
Type: single nucleotide variant
Location: chr10:17233856 (GRCh38)
Gene constraint: LOEUF 0.542 · pLI 0.86 (gnomAD)
Structure: AlphaFold pLDDT 78.05 · 26 PDB
Residue 269: an α-helix; the if rod domain; the 'coil 2' region

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-p-leu269 (accessed [today's date]).

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