Is COL24A1 p.Pro965Ser (c.2893C>T) pathogenic?

COL24A1 p.Pro965Ser (c.2893C>T) is classified Uncertain significance in COL24A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-26). AlphaMissense: likely benign (0.0885); Ultra-rare (popmax 0.0107%, afr).

How common is COL24A1 p.Pro965Ser (c.2893C>T) in the general population?

COL24A1 p.Pro965Ser (c.2893C>T) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

What do computational predictors say about COL24A1 p.Pro965Ser (c.2893C>T)?

AlphaMissense predicts likely benign (score 0.0885) — an in-silico prediction, not a clinical call.

COL24A1 p.Pro965Ser

c.2893C>T · rs554002514 · VCV2303557

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0885 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0885	likely benign
REVEL	0.408	indeterminate
SaProt	LLR -7.84	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 2.5	GERP 0.14, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 426 kb · p 0.17 · regional, not allelic
Overall
CADD	19.79	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 0.0107% African / African-American · 8/74,726 alleles

Filtering AF 0.00529% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.000684% 11/1,608,966 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0107%	9,341
Admixed American	0.00337%	29,675
Remaining individualsnot grpmax-eligible	0.00161%	62,240

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.Pro965Ser
Coding: c.2893C>T
MANE Select: NM_152890
dbSNP: rs554002514
Type: single nucleotide variant
Location: chr1:85895887 (GRCh38)
Gene constraint: LOEUF 0.956 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 49.59
Residue 965: the collagen-like 8 domain; the 'disordered' region

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-pro965ser (accessed [today's date]).

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