Is COL5A1 p.Ser84= (c.252C>T) pathogenic?

COL5A1 p.Ser84= (c.252C>T) is classified Benign/Likely benign in COL5A1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-12-01). Rare (popmax 0.163%, afr); Associated with fibromuscular dysplasia, multifocal.

What condition is associated with COL5A1 p.Ser84= (c.252C>T)?

COL5A1 p.Ser84= (c.252C>T) is associated with fibromuscular dysplasia, multifocal, Ehlers-Danlos syndrome, classic type, Ehlers-Danlos syndrome, classic type, 1 (ClinVar).

How common is COL5A1 p.Ser84= (c.252C>T) in the general population?

COL5A1 p.Ser84= (c.252C>T) is rare (popmax 0.163%, afr) (gnomAD).

COL5A1 p.Ser84=

c.252C>T · rs151293601 · VCV136917

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.163%, afr)

Conditions

fibromuscular dysplasia, multifocal

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 -5.7	GERP -4.3
Overall
CADD	10.26	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.163% African / African-American · 122/75,064 alleles

Filtering AF 0.139% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.13%

Overall 0.012% 194/1,613,492 alleles · rare exomes 98/1,461,104 · genomes 96/152,388 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.163%	615
East Asian	0.0468%	2,138
Admixed American	0.02%	5,003
Remaining individualsnot grpmax-eligible	0.0176%	5,681
Middle Eastern	0.0168%	5,956
European (non-Finnish)	0.00229%	43,705

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: COL5A1
Protein: p.Ser84=
Coding: c.252C>T
MANE Select: NM_000093
dbSNP: rs151293601
Type: single nucleotide variant
Location: chr9:134691054 (GRCh38)
Gene constraint: LOEUF 0.089 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 52.54 · 1 PDB
Residue 84: the laminin g-like domain

Full COL5A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

fibromuscular dysplasia, multifocal — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Ehlers-Danlos syndrome, classic type Ehlers-Danlos syndrome, classic type, 1 familial thoracic aortic aneurysm and aortic dissection

Similar variants

COL5A1 p.Ser84Arg Uncertain significance ★ ⚠ same residue
COL5A1 c.1332+1G>T Pathogenic/Likely pathogenic ★★ same condition
COL5A1 c.1720-11T>A Likely pathogenic ★★ same condition
COL5A1 c.2034+1G>A Pathogenic ★★ same condition
COL5A1 c.2430+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL5A1 c.2430+1G>C Pathogenic ★★ same condition
COL5A1 c.2701-25T>G Pathogenic ★★ same condition
COL5A1 c.4338+1G>A 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/col5a1-p-ser84 (accessed [today's date]).

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