Is COL4A1 p.Pro587Ser (c.1759C>T) pathogenic?

COL4A1 p.Pro587Ser (c.1759C>T) is classified Uncertain significance in COL4A1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-27). AlphaMissense: likely benign (0.0899); Absent from gnomAD v4.1.

How common is COL4A1 p.Pro587Ser (c.1759C>T) in the general population?

COL4A1 p.Pro587Ser (c.1759C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COL4A1 p.Pro587Ser (c.1759C>T)?

AlphaMissense predicts likely benign (score 0.0899) — an in-silico prediction, not a clinical call.

COL4A1 p.Pro587Ser

c.1759C>T · rs1258641245 · VCV2803276

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0899 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,950)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0899	likely benign
REVEL	0.57	indeterminate
SaProt	LLR -5.99	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 7.5	GERP 1.8, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 30 kb · p 1.5e-10 · regional, not allelic
Overall
CADD	21.5	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

No allele count reported in gnomAD v4.1 (AN 1,613,950). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: COL4A1
Protein: p.Pro587Ser
Coding: c.1759C>T
MANE Select: NM_001845
dbSNP: rs1258641245
Type: single nucleotide variant
Location: chr13:110186523 (GRCh38)
Gene constraint: LOEUF 0.238 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 49.43 · 4 PDB
Residue 587: a modified residue (3-hydroxyproline); the 'triple-helical region' region; the 'disordered' region

Full COL4A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COL4A1 p.Pro587Ala Uncertain significance ★★ ⚠ same residue
COL4A1 c.1085-2A>G Likely pathogenic ★★ same type
COL4A1 c.1991-2A>G Likely pathogenic ★★ same type
COL4A1 c.2458+1G>A Pathogenic ★★ same type
COL4A1 c.2458+2T>C Pathogenic/Likely pathogenic ★★ same type
COL4A1 c.3742+1G>A Pathogenic ★★ same type
COL4A1 c.388-1G>C Pathogenic/Likely pathogenic ★★ same type
COL4A1 c.4150+1G>A Pathogenic ★★ 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/col4a1-p-pro587ser (accessed [today's date]).

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