Is COL19A1 p.Pro573Ser (c.1717C>T) pathogenic?

COL19A1 p.Pro573Ser (c.1717C>T) is classified Uncertain significance in COL19A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-10). AlphaMissense: likely benign (0.0962); Ultra-rare (popmax 0.0166%, mid).

How common is COL19A1 p.Pro573Ser (c.1717C>T) in the general population?

COL19A1 p.Pro573Ser (c.1717C>T) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

What do computational predictors say about COL19A1 p.Pro573Ser (c.1717C>T)?

AlphaMissense predicts likely benign (score 0.0962) — an in-silico prediction, not a clinical call.

COL19A1 p.Pro573Ser

c.1717C>T · rs2482823739 · VCV2325432

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0962 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0962	likely benign
REVEL	0.681	pathogenic-leaning
SaProt	LLR -9.12	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 328 kb · p 0.71 · regional, not allelic
Overall
CADD	24.3	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

Grpmax group 0.0166% Middle Eastern · 1/6,020 alleles

Overall 6.94e-05% 1/1,441,072 alleles · ultra-rare

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: COL19A1
Protein: p.Pro573Ser
Coding: c.1717C>T
MANE Select: NM_001858
dbSNP: rs2482823739
Type: single nucleotide variant
Location: chr6:70144954 (GRCh38)
Gene constraint: LOEUF 0.876 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.83
Residue 573: the 'disordered' region; the 'triple-helical region 3 (col3)' region; the collagen-like 5 domain

Full COL19A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COL19A1 p.Ala1046Thr Uncertain significance ★ ⚠ same type
COL19A1 p.Ala1101Val Uncertain significance ★ ⚠ same type
COL19A1 p.Ala1110Thr Uncertain significance ★ ⚠ same type
COL19A1 p.Ala148Asp Uncertain significance ★ ⚠ same type
COL19A1 p.Ala193Val Uncertain significance ★ ⚠ same type
COL19A1 p.Ala238Pro Uncertain significance ★ ⚠ same type
COL19A1 p.Ala277Gly Uncertain significance ★ ⚠ same type
COL19A1 p.Ala294Thr Uncertain significance ★ ⚠ same type

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/col19a1-p-pro573ser (accessed [today's date]).

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