Is COL15A1 p.Pro623Ser (c.1867C>T) pathogenic?

COL15A1 p.Pro623Ser (c.1867C>T) is classified Uncertain significance in COL15A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-17). AlphaMissense: likely benign (0.1921); Very rare (popmax 0.00223%, eas).

How common is COL15A1 p.Pro623Ser (c.1867C>T) in the general population?

COL15A1 p.Pro623Ser (c.1867C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about COL15A1 p.Pro623Ser (c.1867C>T)?

AlphaMissense predicts likely benign (score 0.1921) — an in-silico prediction, not a clinical call.

COL15A1 p.Pro623Ser

c.1867C>T · rs1839093810 · VCV3147226

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1921 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1921	likely benign
REVEL	0.33	indeterminate
SaProt	LLR -12.02	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 126 kb · p 0.29 · regional, not allelic
Overall
CADD	26.1	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 0.00223% East Asian · 1/44,894 alleles

Overall 0.000186% 3/1,613,538 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,894
African / African-American	0.00133%	74,920
European (non-Finnish)	8.48e-05%	1,179,766

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.Pro623Ser
Coding: c.1867C>T
MANE Select: NM_001855
dbSNP: rs1839093810
Type: single nucleotide variant
Location: chr9:99024886 (GRCh38)
Gene constraint: LOEUF 0.763 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.68 · 1 PDB
Residue 623: the collagen-like 1 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

Similar variants

COL15A1 p.Leu756= Benign ★★ same type
COL15A1 p.Pro1063Leu Benign ★★ same type
COL15A1 p.Ser218= Benign ★★ same type
COL15A1 p.Ala1006Ser Uncertain significance ★ ⚠ same type
COL15A1 p.Ala1115Val Uncertain significance ★ ⚠ same type
COL15A1 p.Ala1148Thr Uncertain significance ★ ⚠ same type
COL15A1 p.Ala1193Val Uncertain significance ★ ⚠ same type
COL15A1 p.Ala1244Ser 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/col15a1-p-pro623ser (accessed [today's date]).

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