Is COL19A1 p.Pro402Arg (c.1205C>G) pathogenic?

COL19A1 p.Pro402Arg (c.1205C>G) is classified Uncertain significance in COL19A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-11). AlphaMissense: likely benign (0.1058); Ultra-rare (popmax 0.047%, eas).

How common is COL19A1 p.Pro402Arg (c.1205C>G) in the general population?

COL19A1 p.Pro402Arg (c.1205C>G) is ultra-rare (popmax 0.047%, eas) (gnomAD).

What do computational predictors say about COL19A1 p.Pro402Arg (c.1205C>G)?

AlphaMissense predicts likely benign (score 0.1058) — an in-silico prediction, not a clinical call.

COL19A1 p.Pro402Arg

c.1205C>G · rs562804000 · VCV3147327

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1058 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.047%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1058	likely benign
REVEL	0.464	indeterminate
SaProt	LLR -9.87	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 328 kb · p 0.71 · regional, not allelic
Overall
CADD	22.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.047% East Asian · 21/44,666 alleles

Filtering AF 0.0315% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0264%

Overall 0.0015% 24/1,600,576 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.047%	2,127
Remaining individualsnot grpmax-eligible	0.00484%	20,677

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.Pro402Arg
Coding: c.1205C>G
MANE Select: NM_001858
dbSNP: rs562804000
Type: single nucleotide variant
Location: chr6:70068457 (GRCh38)
Gene constraint: LOEUF 0.876 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.83
Residue 402: the 'disordered' region; the 'triple-helical region 2 (col2)' region; the collagen-like 3 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-pro402arg (accessed [today's date]).

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