Is COL15A1 p.Ser191Pro (c.571T>C) pathogenic?

COL15A1 p.Ser191Pro (c.571T>C) is classified Benign in COL15A1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-07). AlphaMissense: likely benign (0.0689); Low-frequency (popmax 1.64%, afr); Associated with COL15A1-related disorder.

What condition is associated with COL15A1 p.Ser191Pro (c.571T>C)?

COL15A1 p.Ser191Pro (c.571T>C) is associated with COL15A1-related disorder (ClinVar).

How common is COL15A1 p.Ser191Pro (c.571T>C) in the general population?

COL15A1 p.Ser191Pro (c.571T>C) is low-frequency (popmax 1.64%, afr) (gnomAD).

What do computational predictors say about COL15A1 p.Ser191Pro (c.571T>C)?

AlphaMissense predicts likely benign (score 0.0689) — an in-silico prediction, not a clinical call.

COL15A1 p.Ser191Pro

c.571T>C · rs113791685 · VCV3043699

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0689 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.64%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

COL15A1-related disorder

Computational evidence

Protein change
AlphaMissense	0.0689	likely benign
REVEL	0.01	strongly benign-leaning
SaProt	LLR -5.74	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 -0.58	GERP -3.6
Regional constraint	o/e 0.98	unconstrained · MANE · 126 kb · p 0.29 · regional, not allelic
Overall
CADD	0.131	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 1.64% African / African-American · 1,230/75,032 alleles

Filtering AF 1.56% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.53%

Overall 0.0849% 1,371/1,614,096 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.64%	61
Admixed American	0.123%	811
Remaining individualsnot grpmax-eligible	0.0896%	1,116
Middle Eastern	0.0165%	6,062
South Asian	0.00439%	22,767
European (non-Finnish)	0.000508%	196,672

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.Ser191Pro
Coding: c.571T>C
MANE Select: NM_001855
dbSNP: rs113791685
Type: single nucleotide variant
Location: chr9:98986035 (GRCh38)
Gene constraint: LOEUF 0.763 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.68 · 1 PDB
Residue 191: the laminin g-like domain

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-ser191pro (accessed [today's date]).

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