Is COL15A1 p.Phe69= (c.207C>T) pathogenic?

COL15A1 p.Phe69= (c.207C>T) is classified Likely benign in COL15A1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-12). Very rare (popmax 0.00833%, amr); Associated with COL15A1-related disorder.

What condition is associated with COL15A1 p.Phe69= (c.207C>T)?

COL15A1 p.Phe69= (c.207C>T) is associated with COL15A1-related disorder (ClinVar).

How common is COL15A1 p.Phe69= (c.207C>T) in the general population?

COL15A1 p.Phe69= (c.207C>T) is very rare (popmax 0.00833%, amr) (gnomAD).

COL15A1 p.Phe69=

c.207C>T · rs770970455 · VCV3034011

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Conditions

COL15A1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -12	GERP -3.6
Overall
CADD	0.377	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00833% Admixed American · 5/60,006 alleles

Filtering AF 0.00386% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00353%

Overall 0.00415% 67/1,614,120 alleles · very rare exomes 63/1,461,882 · genomes 4/152,238 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	12,001
European (non-Finnish)	0.00492%	20,346
African / African-American	0.004%	24,981
East Asian	0.00223%	44,900

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: COL15A1
Protein: p.Phe69=
Coding: c.207C>T
MANE Select: NM_001855
dbSNP: rs770970455
Type: single nucleotide variant
Location: chr9:98985671 (GRCh38)
Gene constraint: LOEUF 0.763 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.68 · 1 PDB
Residue 69: the laminin g-like domain

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

Disease context

COL15A1-related disorder

Similar variants

COL15A1 c.100+9C>A Likely benign same condition
COL15A1 c.1761+6A>G Benign same condition
COL15A1 c.1762-6T>C Benign same condition
COL15A1 c.1762-9T>C Likely benign same condition
COL15A1 c.3402+10A>G Likely benign same condition
COL15A1 c.952+9G>A Benign same condition
COL15A1 p.Ala1148= Likely benign same condition
COL15A1 p.Ala1148Val Benign ⚠ 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/col15a1-p-phe69 (accessed [today's date]).

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