Is COL1A1 p.Cys61Trp (c.183C>G) pathogenic?

COL1A1 p.Cys61Trp (c.183C>G) is classified Pathogenic in COL1A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-05). AlphaMissense: likely pathogenic (0.9993); Absent from gnomAD v4.1; Associated with osteogenesis imperfecta type 1.

What condition is associated with COL1A1 p.Cys61Trp (c.183C>G)?

COL1A1 p.Cys61Trp (c.183C>G) is associated with osteogenesis imperfecta type 1 (ClinVar).

How common is COL1A1 p.Cys61Trp (c.183C>G) in the general population?

COL1A1 p.Cys61Trp (c.183C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COL1A1 p.Cys61Trp (c.183C>G)?

AlphaMissense predicts likely pathogenic (score 0.9993) — an in-silico prediction, not a clinical call.

COL1A1 p.Cys61Trp

c.183C>G · rs755126464 · VCV1395929

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9993 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

osteogenesis imperfecta type 1

Computational evidence

Protein change
AlphaMissense	0.9993	likely pathogenic ✓ concordant with ClinVar · top 1% in COL1A1
REVEL	0.798	moderately pathogenic-leaning
SaProt	LLR -16.95	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.36	GERP -3.8, phastCons 0.44
Regional constraint	o/e 0.88	unconstrained · MANE · 3,020 bp · p 0.063 · regional, not allelic
Overall
CADD	22.6	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: COL1A1
Protein: p.Cys61Trp
Coding: c.183C>G
MANE Select: NM_000088
dbSNP: rs755126464
Type: single nucleotide variant
Location: chr17:50199868 (GRCh38)
Gene constraint: LOEUF 0.159 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.26 · 14 PDB
Residue 61: the vwfc domain

Full COL1A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

osteogenesis imperfecta type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

COL1A1 p.Cys61= Benign/Likely benign ★★ same residue
COL1A1 p.Cys61Tyr Pathogenic ★ same residue
COL1A1 c.1003-1G>A Pathogenic/Likely pathogenic ★★ same condition
COL1A1 c.103+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL1A1 c.103+2T>C Pathogenic ★★ same condition
COL1A1 c.104-1G>T Pathogenic/Likely pathogenic ★★ same condition
COL1A1 c.104-2A>G Pathogenic/Likely pathogenic ★★ same condition
COL1A1 c.1056+1G>A Pathogenic ★★ same condition

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/col1a1-p-cys61trp (accessed [today's date]).

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