Is VIM p.Asn456= (c.1368C>T) pathogenic?

VIM p.Asn456= (c.1368C>T) is classified Likely benign in VIM (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-28). Ultra-rare (popmax 0.027%, amr); Associated with cataract 30.

What condition is associated with VIM p.Asn456= (c.1368C>T)?

VIM p.Asn456= (c.1368C>T) is associated with cataract 30 (ClinVar).

How common is VIM p.Asn456= (c.1368C>T) in the general population?

VIM p.Asn456= (c.1368C>T) is ultra-rare (popmax 0.027%, amr) (gnomAD).

VIM p.Asn456=

c.1368C>T · rs753533838 · VCV2766744

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.027%, 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 -2.9	GERP -4
Overall
CADD	4.038	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.027% Admixed American · 16/59,354 alleles

Filtering AF 0.0169% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0137%

Overall 0.00561% 90/1,604,096 alleles · ultra-rare exomes 82/1,452,532 · genomes 8/151,564 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.027%	3,710
African / African-American	0.0107%	9,330
East Asian	0.00892%	11,205
Remaining individualsnot grpmax-eligible	0.00645%	15,506
European (non-Finnish)	0.00485%	20,601
South Asian	0.00111%	89,902

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.Asn456=
Coding: c.1368C>T
MANE Select: NM_003380
dbSNP: rs753533838
Type: single nucleotide variant
Location: chr10:17237238 (GRCh38)
Gene constraint: LOEUF 0.542 · pLI 0.86 (gnomAD)
Structure: AlphaFold pLDDT 78.05 · 26 PDB
Residue 456: the 'tail' 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-asn456 (accessed [today's date]).

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