Is COL24A1 p.Pro581Ser (c.1741C>T) pathogenic?

COL24A1 p.Pro581Ser (c.1741C>T) is classified Uncertain significance in COL24A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-01). AlphaMissense: likely benign (0.0942); Very rare (popmax 0.00706%, nfe).

How common is COL24A1 p.Pro581Ser (c.1741C>T) in the general population?

COL24A1 p.Pro581Ser (c.1741C>T) is very rare (popmax 0.00706%, nfe) (gnomAD).

What do computational predictors say about COL24A1 p.Pro581Ser (c.1741C>T)?

AlphaMissense predicts likely benign (score 0.0942) — an in-silico prediction, not a clinical call.

COL24A1 p.Pro581Ser

c.1741C>T · VCV4005232

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0942 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00706%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0942	likely benign
REVEL	0.09	moderately benign-leaning
SaProt	LLR -8.04	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 5	GERP 1.6, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 426 kb · p 0.17 · regional, not allelic
Overall
CADD	19.73	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 0.00706% European (non-Finnish) · 81/1,148,100 alleles

Filtering AF 0.00578% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00529%

Overall 0.00554% 86/1,551,022 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00706%	14,174
African / African-American	0.0055%	18,179
Remaining individualsnot grpmax-eligible	0.00169%	59,090

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: COL24A1
Protein: p.Pro581Ser
Coding: c.1741C>T
MANE Select: NM_152890
Type: single nucleotide variant
Location: chr1:86063726 (GRCh38)
Gene constraint: LOEUF 0.956 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 49.59
Residue 581: the 'disordered' region; the collagen-like 2 domain

Full COL24A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COL24A1 p.Arg1371Gln Likely benign ★★ same type
COL24A1 p.Leu222= Benign ★★ same type
COL24A1 p.Pro1067Arg Benign ★★ same type
COL24A1 p.Pro896His Benign ★★ ⚠ same type
COL24A1 p.Ser201Asn Benign ★★ ⚠ same type
COL24A1 p.Ala1027Pro Uncertain significance ★ ⚠ same type
COL24A1 p.Ala1223Thr Uncertain significance ★ ⚠ same type
COL24A1 p.Ala1487Thr 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/col24a1-p-pro581ser (accessed [today's date]).

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