Is COL20A1 p.Ser673Phe (c.2018C>T) pathogenic?

COL20A1 p.Ser673Phe (c.2018C>T) is classified Uncertain significance in COL20A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-20). AlphaMissense: likely benign (0.1688); Very rare (popmax 0.00192%, amr).

How common is COL20A1 p.Ser673Phe (c.2018C>T) in the general population?

COL20A1 p.Ser673Phe (c.2018C>T) is very rare (popmax 0.00192%, amr) (gnomAD).

What do computational predictors say about COL20A1 p.Ser673Phe (c.2018C>T)?

AlphaMissense predicts likely benign (score 0.1688) — an in-silico prediction, not a clinical call.

COL20A1 p.Ser673Phe

c.2018C>T · VCV4655519

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1688 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00192%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1688	likely benign
REVEL	0.183	benign-leaning
SaProt	LLR -10.17	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 1.1, phastCons 0.87
Regional constraint	o/e 1.07	unconstrained · MANE · 35 kb · p 0.0022 · regional, not allelic
Overall
CADD	21.4	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 0.00192% Admixed American · 1/52,026 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000193% 3/1,557,214 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00192%	52,026
European (non-Finnish)	0.000174%	575,430

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.Ser673Phe
Coding: c.2018C>T
MANE Select: NM_020882
Type: single nucleotide variant
Location: chr20:63312876 (GRCh38)
Gene constraint: LOEUF 1.419 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.88 · 4 PDB
Residue 673: the fibronectin type-iii 5 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-ser673phe (accessed [today's date]).

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