Is COL20A1 p.Ala35Pro (c.103G>C) pathogenic?

COL20A1 p.Ala35Pro (c.103G>C) is classified Uncertain significance in COL20A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-11). AlphaMissense: ambiguous (0.5263); Ultra-rare (popmax 0.0173%, afr).

How common is COL20A1 p.Ala35Pro (c.103G>C) in the general population?

COL20A1 p.Ala35Pro (c.103G>C) is ultra-rare (popmax 0.0173%, afr) (gnomAD).

What do computational predictors say about COL20A1 p.Ala35Pro (c.103G>C)?

AlphaMissense predicts ambiguous (score 0.5263) — an in-silico prediction, not a clinical call.

COL20A1 p.Ala35Pro

c.103G>C · rs373850387 · VCV2570266

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5263 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0173%, afr)

Computational evidence

Protein change
AlphaMissense	0.5263	ambiguous
REVEL	0.323	indeterminate
SaProt	LLR -11.84	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.028	GERP -1.8
Regional constraint	o/e 1.07	unconstrained · MANE · 35 kb · p 0.0022 · regional, not allelic
Overall
CADD	8.436	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 0.0173% African / African-American · 13/74,948 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00812%

Overall 0.00112% 18/1,613,270 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0173%	5,765
Remaining individualsnot grpmax-eligible	0.0048%	20,819
South Asian	0.0011%	91,092
European (non-Finnish)	8.48e-05%	1,179,832

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.Ala35Pro
Coding: c.103G>C
MANE Select: NM_020882
dbSNP: rs373850387
Type: single nucleotide variant
Location: chr20:63297930 (GRCh38)
Gene constraint: LOEUF 1.419 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.88 · 4 PDB
Residue 35: the fibronectin type-iii 1 domain

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

Similar variants

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
COL20A1 p.Ala312Thr 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-ala35pro (accessed [today's date]).

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