Is COL11A1 p.Ser1573Pro (c.4717T>C) pathogenic?

COL11A1 p.Ser1573Pro (c.4717T>C) is classified Conflicting classifications of pathogenicity in COL11A1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-10-25). AlphaMissense: likely benign (0.1647); Very rare (popmax 0.00667%, afr).

How common is COL11A1 p.Ser1573Pro (c.4717T>C) in the general population?

COL11A1 p.Ser1573Pro (c.4717T>C) is very rare (popmax 0.00667%, afr) (gnomAD).

What do computational predictors say about COL11A1 p.Ser1573Pro (c.4717T>C)?

AlphaMissense predicts likely benign (score 0.1647) — an in-silico prediction, not a clinical call.

COL11A1 p.Ser1573Pro

c.4717T>C · rs865904271 · VCV1304994

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1647 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1647	likely benign
REVEL	0.486	indeterminate
SaProt	LLR -9.44	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 3.2	GERP -2.1, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 230 kb · p 0.038 · regional, not allelic
Overall
CADD	17.01	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 0.00667% African / African-American · 5/74,914 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.000434% 7/1,613,830 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00667%	14,983
European (non-Finnish)	0.00017%	589,946

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: COL11A1
Protein: p.Ser1573Pro
Coding: c.4717T>C
MANE Select: NM_001854
dbSNP: rs865904271
Type: single nucleotide variant
Location: chr1:102886948 (GRCh38)
Gene constraint: LOEUF 0.349 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 53.06

Full COL11A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COL11A1 p.Ser1573= Conflicting classifications of pathogenicity ★ same residue
COL11A1 p.Ser1573Ala Uncertain significance ★ ⚠ same residue
COL11A1 p.Ser1573Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
COL11A1 c.1245+1G>A Pathogenic/Likely pathogenic ★★ same type
COL11A1 c.1245+1G>T Pathogenic/Likely pathogenic ★★ same type
COL11A1 c.1629+1G>A Likely pathogenic ★★ same type
COL11A1 c.1630-1G>T Pathogenic ★★ same type
COL11A1 c.1791+1G>T Likely pathogenic ★★ 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/col11a1-p-ser1573pro (accessed [today's date]).

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