Is VIM p.Ser49Asn (c.146G>A) pathogenic?

VIM p.Ser49Asn (c.146G>A) is classified Uncertain significance in VIM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-02). AlphaMissense: likely benign (0.1919); Very rare (popmax 8.48e-05%, nfe).

How common is VIM p.Ser49Asn (c.146G>A) in the general population?

VIM p.Ser49Asn (c.146G>A) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about VIM p.Ser49Asn (c.146G>A)?

AlphaMissense predicts likely benign (score 0.1919) — an in-silico prediction, not a clinical call.

VIM p.Ser49Asn

c.146G>A · VCV4603697

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1919 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1919	likely benign
REVEL	0.435	indeterminate
SaProt	LLR -12.32	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP -2.4, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 255 bp · p 0.5 · regional, not allelic
Overall
CADD	19.96	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

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,178,694 alleles

Overall 6.22e-05% 1/1,608,906 alleles · very rare exomes 1/1,456,666 · genomes 0/152,240 · joint denominator

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.Ser49Asn
Coding: c.146G>A
MANE Select: NM_003380
Type: single nucleotide variant
Location: chr10:17229568 (GRCh38)
Gene constraint: LOEUF 0.542 · pLI 0.86 (gnomAD)
Structure: AlphaFold pLDDT 78.05 · 26 PDB
Residue 49: a modified residue (phosphoserine); the 'head' region

Full VIM gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

VIM p.Ser49Arg Uncertain significance ★ ⚠ same residue
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-ser49asn (accessed [today's date]).

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