Is COL5A2 p.Pro325= (c.975C>T) pathogenic?

COL5A2 p.Pro325= (c.975C>T) is classified Benign/Likely benign in COL5A2 (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-01-26). Low-frequency (popmax 2.52%, afr); Associated with Ehlers-Danlos syndrome.

What condition is associated with COL5A2 p.Pro325= (c.975C>T)?

COL5A2 p.Pro325= (c.975C>T) is associated with Ehlers-Danlos syndrome, Ehlers-Danlos syndrome, classic type, 1, Ehlers-Danlos syndrome, classic type, 2 (ClinVar).

How common is COL5A2 p.Pro325= (c.975C>T) in the general population?

COL5A2 p.Pro325= (c.975C>T) is low-frequency (popmax 2.52%, afr) (gnomAD).

COL5A2 p.Pro325=

c.975C>T · rs144344474 · VCV136932

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.52%, afr)

Conditions

Ehlers-Danlos syndrome

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 0.4	GERP -3, phastCons 0.74
Overall
CADD	6.849	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.52% African / African-American · 1,890/74,930 alleles

Filtering AF 2.43% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.39%

Overall 0.161% 2,598/1,612,866 alleles · low-frequency exomes 1,522/1,460,688 · genomes 1,076/152,178 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.52%	40
Middle Eastern	0.792%	126
Remaining individualsnot grpmax-eligible	0.269%	372
Admixed American	0.147%	681
Ashkenazi Jewishnot grpmax-eligible	0.145%	688
European (non-Finnish)	0.0293%	3,418
South Asian	0.0176%	5,690

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: COL5A2
Protein: p.Pro325=
Coding: c.975C>T
MANE Select: NM_000393
dbSNP: rs144344474
Type: single nucleotide variant
Location: chr2:189079093 (GRCh38)
Gene constraint: LOEUF 0.106 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 53.15
Residue 325: the 'disordered' region

Full COL5A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Ehlers-Danlos syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Ehlers-Danlos syndrome, classic type, 1 Ehlers-Danlos syndrome, classic type, 2 familial thoracic aortic aneurysm and aortic dissection

Similar variants

COL5A2 c.1159-1G>A Likely pathogenic ★★ same condition
COL5A2 c.369+1G>T Likely pathogenic ★★ same condition
COL5A2 p.Gly252Cys Pathogenic/Likely pathogenic ★★ same condition
COL5A2 p.Pro659= Pathogenic ★★ same condition
COL5A2 c.1005+4T>C Uncertain significance ★★ same condition
COL5A2 c.1618-7G>A Uncertain significance ★★ same condition
COL5A2 c.1716+5G>A Uncertain significance ★★ same condition
COL5A2 c.1717-3C>T Uncertain significance ★★ 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/col5a2-p-pro325 (accessed [today's date]).

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