Is COL20A1 p.Arg103Pro (c.308G>C) pathogenic?

COL20A1 p.Arg103Pro (c.308G>C) is classified Uncertain significance in COL20A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-28). AlphaMissense: likely benign (0.1016); Ultra-rare (popmax 0.0472%, eas).

How common is COL20A1 p.Arg103Pro (c.308G>C) in the general population?

COL20A1 p.Arg103Pro (c.308G>C) is ultra-rare (popmax 0.0472%, eas) (gnomAD).

What do computational predictors say about COL20A1 p.Arg103Pro (c.308G>C)?

AlphaMissense predicts likely benign (score 0.1016) — an in-silico prediction, not a clinical call.

COL20A1 p.Arg103Pro

c.308G>C · rs745660496 · VCV3147373

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1016 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0472%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1016	likely benign
REVEL	0.051	moderately benign-leaning
SaProt	LLR -8.98	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 0.55	GERP -1.5, phastCons 0.007
Regional constraint	o/e 1.07	unconstrained · MANE · 35 kb · p 0.0022 · regional, not allelic
Overall
CADD	5.753	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 0.0472% East Asian · 21/44,472 alleles

Filtering AF 0.0316% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0265%

Overall 0.00137% 22/1,603,924 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0472%	2,118
Remaining individualsnot grpmax-eligible	0.00161%	62,026

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: COL20A1
Protein: p.Arg103Pro
Coding: c.308G>C
MANE Select: NM_020882
dbSNP: rs745660496
Type: single nucleotide variant
Location: chr20:63305531 (GRCh38)
Gene constraint: LOEUF 1.419 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.88 · 4 PDB
Residue 103: the fibronectin type-iii 1 domain

Full COL20A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COL20A1 p.Arg103Cys Uncertain significance ★ ⚠ same residue
COL20A1 p.Thr141= Benign ★★ same type
COL20A1 p.Ala1059Pro Uncertain significance ★ ⚠ same type
COL20A1 p.Ala1063Thr Uncertain significance ★ ⚠ same type
COL20A1 p.Ala1244Ser Uncertain significance ★ ⚠ same type
COL20A1 p.Ala1265Thr Uncertain significance ★ ⚠ same type
COL20A1 p.Ala274Thr Uncertain significance ★ ⚠ same type
COL20A1 p.Ala300Thr 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/col20a1-p-arg103pro (accessed [today's date]).

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