Is VIM p.Ser459fs (c.1374_1375dup) pathogenic?

VIM p.Ser459fs (c.13741375dup) is classified Uncertain significance in VIM (ClinVar, Single submitter, 1 submitter; last evaluated 2019-09-12). Absent from gnomAD; Associated with cataract 30.

What condition is associated with VIM p.Ser459fs (c.1374_1375dup)?

VIM p.Ser459fs (c.1374_1375dup) is associated with cataract 30 (ClinVar).

How common is VIM p.Ser459fs (c.1374_1375dup) in the general population?

VIM p.Ser459fs (c.1374_1375dup) is absent from gnomAD (gnomAD).

VIM p.Ser459fs

c.1374_1375dup · rs1846907790 · VCV962651

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

cataract 30

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (10 of 10) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.9	GERP 2, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: VIM
Protein: p.Ser459fs
Coding: c.1374_1375dup
MANE Select: NM_003380
dbSNP: rs1846907790
Type: Duplication
Location: chr10:17237243 (GRCh38)
Gene constraint: LOEUF 0.542 · pLI 0.86 (gnomAD)
Structure: AlphaFold pLDDT 78.05 · 26 PDB
Residue 459: the 'tail' region; a modified residue (phosphoserine)

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 c.1360-7dup Benign ★ same condition
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

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-ser459fs (accessed [today's date]).

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