Is COL28A1 p.Arg297Pro (c.890G>C) pathogenic?

COL28A1 p.Arg297Pro (c.890G>C) is classified Uncertain significance in COL28A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-22). AlphaMissense: likely benign (0.0974); Ultra-rare (popmax 0.0344%, nfe).

How common is COL28A1 p.Arg297Pro (c.890G>C) in the general population?

COL28A1 p.Arg297Pro (c.890G>C) is ultra-rare (popmax 0.0344%, nfe) (gnomAD).

What do computational predictors say about COL28A1 p.Arg297Pro (c.890G>C)?

AlphaMissense predicts likely benign (score 0.0974) — an in-silico prediction, not a clinical call.

COL28A1 p.Arg297Pro

c.890G>C · rs76334274 · VCV2509530

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0974 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0344%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0974	likely benign
REVEL	0.193	benign-leaning
SaProt	LLR -6.63	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.9	GERP -0.9
Regional constraint	o/e 1.16	unconstrained · MANE · 174 kb · p 8.4e-10 · regional, not allelic
Overall
CADD	13.16	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 0.0344% European (non-Finnish) · 405/1,177,938 alleles

Filtering AF 0.0316% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0305%

Overall 0.0275% 444/1,611,664 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0344%	2,908
Remaining individualsnot grpmax-eligible	0.0272%	3,672
Admixed American	0.0267%	3,748
African / African-American	0.008%	12,498

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: COL28A1
Protein: p.Arg297Pro
Coding: c.890G>C
MANE Select: NM_001037763
dbSNP: rs76334274
Type: single nucleotide variant
Location: chr7:7511128 (GRCh38)
Gene constraint: LOEUF 1.124 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.81
Residue 297: the 'disordered' region

Full COL28A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COL28A1 p.Arg297Cys Uncertain significance ★ ⚠ same residue
COL28A1 c.1792-2A>G Uncertain significance ★ same type
COL28A1 p.Ala1075Asp Uncertain significance ★ ⚠ same type
COL28A1 p.Ala274Thr Uncertain significance ★ ⚠ same type
COL28A1 p.Ala535Gly Uncertain significance ★ ⚠ same type
COL28A1 p.Ala631Asp Uncertain significance ★ ⚠ same type
COL28A1 p.Ala825Val Uncertain significance ★ ⚠ same type
COL28A1 p.Ala864Ser 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/col28a1-p-arg297pro (accessed [today's date]).

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