Is COL15A1 p.Pro577Arg (c.1730C>G) pathogenic?

COL15A1 p.Pro577Arg (c.1730C>G) is classified Uncertain significance in COL15A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-08). AlphaMissense: likely benign (0.0701); Absent from gnomAD v4.1.

How common is COL15A1 p.Pro577Arg (c.1730C>G) in the general population?

COL15A1 p.Pro577Arg (c.1730C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COL15A1 p.Pro577Arg (c.1730C>G)?

AlphaMissense predicts likely benign (score 0.0701) — an in-silico prediction, not a clinical call.

COL15A1 p.Pro577Arg

c.1730C>G · rs377293812 · VCV3147225

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0701 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0701	likely benign
REVEL	0.175	moderately benign-leaning
SaProt	LLR -8.46	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 -0.48	GERP -1.8
Regional constraint	o/e 0.98	unconstrained · MANE · 126 kb · p 0.29 · regional, not allelic
Overall
CADD	1.253	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: COL15A1
Protein: p.Pro577Arg
Coding: c.1730C>G
MANE Select: NM_001855
dbSNP: rs377293812
Type: single nucleotide variant
Location: chr9:99022119 (GRCh38)
Gene constraint: LOEUF 0.763 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.68 · 1 PDB
Residue 577: the 'disordered' region; the 'nonhelical region 2 (nc2)' region

Full COL15A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COL15A1 p.Leu756= Benign ★★ same type
COL15A1 p.Pro1063Leu Benign ★★ same type
COL15A1 p.Ser218= Benign ★★ same type
COL15A1 p.Ala1006Ser Uncertain significance ★ ⚠ same type
COL15A1 p.Ala1115Val Uncertain significance ★ ⚠ same type
COL15A1 p.Ala1148Thr Uncertain significance ★ ⚠ same type
COL15A1 p.Ala1193Val Uncertain significance ★ ⚠ same type
COL15A1 p.Ala1244Ser 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/col15a1-p-pro577arg (accessed [today's date]).

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