Is COL15A1 p.Pro714Ser (c.2140C>T) pathogenic?

COL15A1 p.Pro714Ser (c.2140C>T) is classified Likely benign in COL15A1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-13). AlphaMissense: likely benign (0.089); Rare (popmax 0.561%, afr); Associated with COL15A1-related disorder.

What condition is associated with COL15A1 p.Pro714Ser (c.2140C>T)?

COL15A1 p.Pro714Ser (c.2140C>T) is associated with COL15A1-related disorder (ClinVar).

How common is COL15A1 p.Pro714Ser (c.2140C>T) in the general population?

COL15A1 p.Pro714Ser (c.2140C>T) is rare (popmax 0.561%, afr) (gnomAD).

What do computational predictors say about COL15A1 p.Pro714Ser (c.2140C>T)?

AlphaMissense predicts likely benign (score 0.089) — an in-silico prediction, not a clinical call.

COL15A1 p.Pro714Ser

c.2140C>T · rs142089094 · VCV3033326

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.089 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.561%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

COL15A1-related disorder

Computational evidence

Protein change
AlphaMissense	0.089	likely benign
REVEL	0.542	indeterminate
SaProt	LLR -7.62	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 6.1	GERP 1.9, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 126 kb · p 0.29 · regional, not allelic
Overall
CADD	25.3	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 0.561% African / African-American · 421/74,998 alleles

Filtering AF 0.517% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.5%

Overall 0.0318% 512/1,610,530 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.561%	178
Admixed American	0.0367%	2,728
Remaining individualsnot grpmax-eligible	0.0288%	3,467
Middle Eastern	0.0165%	6,052
European (non-Finnish)	0.00425%	23,539

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: COL15A1
Protein: p.Pro714Ser
Coding: c.2140C>T
MANE Select: NM_001855
dbSNP: rs142089094
Type: single nucleotide variant
Location: chr9:99035074 (GRCh38)
Gene constraint: LOEUF 0.763 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.68 · 1 PDB
Residue 714: the collagen-like 2 domain; the 'disordered' region; the 'triple-helical region 2 (col2)' region

Full COL15A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

COL15A1-related disorder

Similar variants

COL15A1 c.100+9C>A Likely benign same condition
COL15A1 c.1761+6A>G Benign same condition
COL15A1 c.1762-6T>C Benign same condition
COL15A1 c.1762-9T>C Likely benign same condition
COL15A1 c.3402+10A>G Likely benign same condition
COL15A1 c.952+9G>A Benign same condition
COL15A1 p.Ala1148= Likely benign same condition
COL15A1 p.Ala1148Val Benign ⚠ same condition

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/col15a1-p-pro714ser (accessed [today's date]).

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