Is VIM p.Leu387Pro (c.1160T>C) pathogenic?

VIM p.Leu387Pro (c.1160T>C) is classified Likely pathogenic in VIM (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-03). AlphaMissense: likely pathogenic (0.9999); Absent from gnomAD v4.1; Associated with syndrome with premature-aging.

What condition is associated with VIM p.Leu387Pro (c.1160T>C)?

VIM p.Leu387Pro (c.1160T>C) is associated with syndrome with premature-aging (ClinVar).

How common is VIM p.Leu387Pro (c.1160T>C) in the general population?

VIM p.Leu387Pro (c.1160T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about VIM p.Leu387Pro (c.1160T>C)?

AlphaMissense predicts likely pathogenic (score 0.9999) — an in-silico prediction, not a clinical call.

VIM p.Leu387Pro

c.1160T>C · rs1588736025 · VCV692107

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9999 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

syndrome with premature-aging

Computational evidence

Protein change
AlphaMissense	0.9999	likely pathogenic ✓ concordant with ClinVar · top 2% in VIM
REVEL	0.893	moderately pathogenic-leaning
SaProt	LLR -16.60	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 7,480 bp · p 0.038 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: VIM
Protein: p.Leu387Pro
Coding: c.1160T>C
MANE Select: NM_003380
dbSNP: rs1588736025
Type: single nucleotide variant
Location: chr10:17235320 (GRCh38)
Gene constraint: LOEUF 0.542 · pLI 0.86 (gnomAD)
Structure: AlphaFold pLDDT 78.05 · 26 PDB
Residue 387: 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

syndrome with premature-aging

Similar variants

VIM p.Val173Ala Uncertain significance ★ ⚠ same condition
VIM p.Arg45His Uncertain significance ★★ ⚠ same type
VIM p.Asp360Glu Uncertain significance ★★ ⚠ same type
VIM p.Leu164Val Uncertain significance ★★ ⚠ same type
VIM p.Thr458Ala Uncertain significance ★★ ⚠ same type
VIM p.Val272Ile Uncertain significance ★★ ⚠ same type
VIM c.1008+18A>G Benign/Likely benign ★★ same type
VIM c.1008+99G>A Benign ★★ same type

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-leu387pro (accessed [today's date]).

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