Is COL5A2 p.Arg464Pro (c.1391G>C) pathogenic?

COL5A2 p.Arg464Pro (c.1391G>C) is classified Uncertain significance in COL5A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-01). AlphaMissense: ambiguous (0.5385); Absent from gnomAD v4.1.

How common is COL5A2 p.Arg464Pro (c.1391G>C) in the general population?

COL5A2 p.Arg464Pro (c.1391G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COL5A2 p.Arg464Pro (c.1391G>C)?

AlphaMissense predicts ambiguous (score 0.5385) — an in-silico prediction, not a clinical call.

COL5A2 p.Arg464Pro

c.1391G>C · VCV4085665

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5385 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.5385	ambiguous
REVEL	0.571	indeterminate
SaProt	LLR -6.62	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 0.85, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 146 kb · p 1.2e-16 · regional, not allelic
Overall
CADD	26.4	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: COL5A2
Protein: p.Arg464Pro
Coding: c.1391G>C
MANE Select: NM_000393
Type: single nucleotide variant
Location: chr2:189068025 (GRCh38)
Gene constraint: LOEUF 0.106 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 53.15
Residue 464: the 'disordered' region

Full COL5A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COL5A2 p.Arg464Gln Uncertain significance ★ ⚠ same residue
COL5A2 c.1159-1G>A Likely pathogenic ★★ same type
COL5A2 c.2391+5G>A Likely pathogenic ★★ same type
COL5A2 c.369+1G>T Likely pathogenic ★★ same type
COL5A2 p.Gly252Cys Pathogenic/Likely pathogenic ★★ same type
COL5A2 p.Pro659= Pathogenic ★★ same type
COL5A2 c.1005+4T>C Uncertain significance ★★ same type
COL5A2 c.1618-7G>A 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/col5a2-p-arg464pro (accessed [today's date]).

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