Is COL4A5 p.Phe64fs (c.188dup) pathogenic?

COL4A5 p.Phe64fs (c.188dup) is classified Pathogenic in COL4A5 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-06-07). No gnomAD frequency available for this variant; Associated with X-linked Alport syndrome.

What condition is associated with COL4A5 p.Phe64fs (c.188dup)?

COL4A5 p.Phe64fs (c.188dup) is associated with X-linked Alport syndrome (ClinVar).

How common is COL4A5 p.Phe64fs (c.188dup) in the general population?

COL4A5 p.Phe64fs (c.188dup) is no gnomAD frequency available for this variant (gnomAD).

How is Alport syndrome inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

COL4A5 p.Phe64fs

c.188dup · rs1603276159 · VCV807391

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

X-linked Alport syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 3 of 53
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.71	GERP -2.1, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: COL4A5
Protein: p.Phe64fs
Coding: c.188dup
MANE Select: NM_033380
dbSNP: rs1603276159
Type: Duplication
Location: chrX:108559108 (GRCh38)
Structure: AlphaFold pLDDT 49.04 · 2 PDB
Residue 64: the 'triple-helical region' region; the 'disordered' region

Full COL4A5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

X-linked Alport syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Alport syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked dominant
Onset: Adolescent, Adult, Childhood, Elderly

Similar variants

COL4A5 c.546+2dup Pathogenic ★★ same condition
COL4A5 c.81+2dup Pathogenic ★★ same condition
COL4A5 p.Asn670Ter Pathogenic/Likely pathogenic ★★ same condition
COL4A5 p.Gly1196fs Pathogenic/Likely pathogenic ★★ same condition
COL4A5 c.1032+17dup Benign ★★ same condition
COL4A5 c.2396-5_2396-1dup Likely pathogenic ★ same condition
COL4A5 c.(3373+1_3374-1 Likely pathogenic ★ same condition
COL4A5 p.Arg1319fs 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/col4a5-p-phe64fs (accessed [today's date]).

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