Is VIM c.*247C>T pathogenic?

VIM c.247C>T is classified Benign in VIM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-06-28). Common (popmax 27.3%, nfe) — too common for a highly-penetrant pathogenic allele.

VIM c.*247C>T

Q: How common is VIM c.*247C>T in the general population?

VIM c.*247C>T is common (popmax 27.3%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs3249 · VCV1288184

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 27.3%, nfe) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.4	GERP 0.18, phastCons 1
Non-coding constraint	Z -0.97	1 kb window · o/e 1.07 · regional · uncalibrated
Overall
CADD	13.04	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 27.3% European (non-Finnish) · 69,528/254,836 alleles

Filtering AF 27.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 27%

Overall 21.3% 96,189/452,060 alleles · common exomes 67,651/300,116 · genomes 28,538/151,944 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	35%	3
European (non-Finnish)grpmax	27.3%	4
Finnishnot grpmax-eligible	21.9%	5
Remaining individualsnot grpmax-eligible	21.2%	5
Admixed American	16.3%	6
Ashkenazi Jewishnot grpmax-eligible	15.5%	6
Middle Eastern	13.2%	8
South Asian	10.3%	10
African / African-American	8.05%	12
East Asian	6.47%	15

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.*247C>T
MANE Select: NM_003380
dbSNP: rs3249
Type: single nucleotide variant
Location: chr10:17237518 (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

Similar variants

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
VIM c.1009-10C>T 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-c-star-247c-t (accessed [today's date]).

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