Is COL1A1 p.Gly467Glu (c.1400G>A) pathogenic?

COL1A1 p.Gly467Glu (c.1400G>A) is classified Likely pathogenic in COL1A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-25). AlphaMissense: likely pathogenic (0.9958); Absent from gnomAD v4.1; Associated with Caffey disease.

What condition is associated with COL1A1 p.Gly467Glu (c.1400G>A)?

COL1A1 p.Gly467Glu (c.1400G>A) is associated with Caffey disease (ClinVar).

How common is COL1A1 p.Gly467Glu (c.1400G>A) in the general population?

COL1A1 p.Gly467Glu (c.1400G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COL1A1 p.Gly467Glu (c.1400G>A)?

AlphaMissense predicts likely pathogenic (score 0.9958) — an in-silico prediction, not a clinical call.

COL1A1 p.Gly467Glu

c.1400G>A · rs267604943 · VCV1526274

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9958 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Caffey disease

Computational evidence

Protein change
AlphaMissense	0.9958	likely pathogenic ✓ concordant with ClinVar · top 6% in COL1A1
REVEL	0.89	moderately pathogenic-leaning
SaProt	LLR -13.50	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.61	unconstrained · MANE · 8,265 bp · p 3e-38 · regional, not allelic
Overall
CADD	27.4	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: COL1A1
Protein: p.Gly467Glu
Coding: c.1400G>A
MANE Select: NM_000088
dbSNP: rs267604943
Type: single nucleotide variant
Location: chr17:50194782 (GRCh38)
Gene constraint: LOEUF 0.159 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.26 · 14 PDB
Residue 467: the 'disordered' region; the 'triple-helical region' region

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

Disease context

Caffey disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

COL1A1 p.Gly467Arg Likely pathogenic ★★ same residue
COL1A1 p.Gly467Ala Pathogenic ★ same residue
COL1A1 c.1299+1G>A Pathogenic ★★ same condition
COL1A1 c.1821+1G>A Pathogenic ★★ same condition
COL1A1 c.2343+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL1A1 p.Arg1014Cys Pathogenic ★★ same condition
COL1A1 p.Arg1026Ter Pathogenic ★★ same condition
COL1A1 p.Arg312Cys Pathogenic/Likely 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-gly467glu (accessed [today's date]).

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