Is COL4A5 p.Pro712Arg (c.2135C>G) pathogenic?

COL4A5 p.Pro712Arg (c.2135C>G) is classified Uncertain significance in COL4A5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-12). AlphaMissense: likely benign (0.1175); Very rare (popmax 0.000126%, nfe).

How common is COL4A5 p.Pro712Arg (c.2135C>G) in the general population?

COL4A5 p.Pro712Arg (c.2135C>G) is very rare (popmax 0.000126%, nfe) (gnomAD).

What do computational predictors say about COL4A5 p.Pro712Arg (c.2135C>G)?

AlphaMissense predicts likely benign (score 0.1175) — an in-silico prediction, not a clinical call.

COL4A5 p.Pro712Arg

c.2135C>G · rs2524329006 · VCV2504191

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1175 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000126%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1175	likely benign
REVEL	0.729	pathogenic-leaning
SaProt	LLR -9.95	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP 1.9, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 256 kb · p 6e-09 · regional, not allelic
Overall
CADD	23.5	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 0.000126% European (non-Finnish) · 1/795,883 alleles

Overall 9.18e-05% 1/1,089,814 alleles · very rare exomes 1/975,930 · genomes 0/113,884 · joint denominator

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: COL4A5
Protein: p.Pro712Arg
Coding: c.2135C>G
MANE Select: NM_033380
dbSNP: rs2524329006
Type: single nucleotide variant
Location: chrX:108601978 (GRCh38)
Structure: AlphaFold pLDDT 49.04 · 2 PDB
Residue 712: the 'triple-helical region' region; the 'disordered' region

Full COL4A5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COL4A5 p.Pro712Thr Uncertain significance ★ ⚠ same residue
COL4A5 c.1032+1G>C Pathogenic/Likely pathogenic ★★ same type
COL4A5 c.1033-1G>A Pathogenic ★★ same type
COL4A5 c.1033-2A>G Pathogenic/Likely pathogenic ★★ same type
COL4A5 c.1339+1G>A Pathogenic/Likely pathogenic ★★ same type
COL4A5 c.141+1G>A Pathogenic ★★ same type
COL4A5 c.1423+1G>A Pathogenic ★★ same type
COL4A5 c.1424-20T>A Pathogenic/Likely 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/col4a5-p-pro712arg (accessed [today's date]).

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