Is VCL p.Ser958Pro (c.2872T>C) pathogenic?

VCL p.Ser958Pro (c.2872T>C) is classified Uncertain significance in VCL (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-10). AlphaMissense: likely benign (0.0843); Absent from gnomAD v4.1.

How common is VCL p.Ser958Pro (c.2872T>C) in the general population?

VCL p.Ser958Pro (c.2872T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about VCL p.Ser958Pro (c.2872T>C)?

AlphaMissense predicts likely benign (score 0.0843) — an in-silico prediction, not a clinical call.

VCL p.Ser958Pro

c.2872T>C · VCV4976388

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0843 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0843	likely benign
REVEL	0.112	moderately benign-leaning
SaProt	LLR -5.18	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP -0.76, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 2,946 bp · p 0.6 · regional, not allelic
Overall
CADD	18.17	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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: VCL
Protein: p.Ser958Pro
Coding: c.2872T>C
MANE Select: NM_014000
Type: single nucleotide variant
Location: chr10:74112035 (GRCh38)
Gene constraint: LOEUF 0.461 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.69 · 37 PDB
Residue 958: the 'c-terminal tail' region

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

Similar variants

VCL p.Ser958Phe Uncertain significance ★ ⚠ same residue
VCL c.1176+4G>C Uncertain significance ★★ same type
VCL c.1352+5G>A Uncertain significance ★★ same type
VCL c.1543+1G>T Uncertain significance ★★ same type
VCL c.1543+4A>G Uncertain significance ★★ same type
VCL c.1743+6A>G Uncertain significance ★★ same type
VCL c.1744-1G>T Uncertain significance ★★ same type
VCL c.2022+5G>T Uncertain significance ★★ 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/vcl-p-ser958pro (accessed [today's date]).

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