Is COL4A5 p.Pro1014Arg (c.3041C>G) pathogenic?

COL4A5 p.Pro1014Arg (c.3041C>G) is classified Uncertain significance in COL4A5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-06-01). AlphaMissense: likely benign (0.1006); Very rare (popmax 0.00258%, nfe); Associated with Inborn genetic diseases.

What condition is associated with COL4A5 p.Pro1014Arg (c.3041C>G)?

COL4A5 p.Pro1014Arg (c.3041C>G) is associated with Inborn genetic diseases (ClinVar).

How common is COL4A5 p.Pro1014Arg (c.3041C>G) in the general population?

COL4A5 p.Pro1014Arg (c.3041C>G) is very rare (popmax 0.00258%, nfe) (gnomAD).

What do computational predictors say about COL4A5 p.Pro1014Arg (c.3041C>G)?

AlphaMissense predicts likely benign (score 0.1006) — an in-silico prediction, not a clinical call.

COL4A5 p.Pro1014Arg

c.3041C>G · rs1407970012 · VCV2166888

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1006 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00258%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1006	likely benign
REVEL	0.554	indeterminate
SaProt	LLR -11.31	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 5.9	GERP 0.11, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 256 kb · p 6e-09 · regional, not allelic
Overall
CADD	23.4	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 0.00258% European (non-Finnish) · 23/891,285 alleles

Filtering AF 0.00172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00144%

Overall 0.0022% 24/1,093,157 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00258%	38,752
Remaining individualsnot grpmax-eligible	0.00211%	47,441

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.Pro1014Arg
Coding: c.3041C>G
MANE Select: NM_033380
dbSNP: rs1407970012
Type: single nucleotide variant
Location: chrX:108625729 (GRCh38)
Structure: AlphaFold pLDDT 49.04 · 2 PDB
Residue 1014: the 'triple-helical region' region; the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

COL4A5 p.Pro1014Leu Uncertain significance ★ ⚠ same residue
COL4A5 c.546+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL4A5 p.Gly135Val Likely pathogenic ★★ same condition
COL4A5 p.Gly426Arg Pathogenic/Likely pathogenic ★★ same condition
COL4A5 p.Arg1319Trp Uncertain significance ★★ ⚠ same condition
COL4A5 p.Arg1518His Uncertain significance ★★ ⚠ same condition
COL4A5 p.Arg1631His Uncertain significance ★★ ⚠ same condition
COL4A5 p.Arg862Gly Uncertain significance ★★ ⚠ 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/col4a5-p-pro1014arg (accessed [today's date]).

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