Is COL4A4 p.Pro263Arg (c.788C>G) pathogenic?

COL4A4 p.Pro263Arg (c.788C>G) is classified Conflicting classifications of pathogenicity in COL4A4 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-19). AlphaMissense: likely benign (0.1297); Ultra-rare (popmax 0.0187%, afr); Associated with glomerulonephritis.

What condition is associated with COL4A4 p.Pro263Arg (c.788C>G)?

COL4A4 p.Pro263Arg (c.788C>G) is associated with glomerulonephritis (ClinVar).

How common is COL4A4 p.Pro263Arg (c.788C>G) in the general population?

COL4A4 p.Pro263Arg (c.788C>G) is ultra-rare (popmax 0.0187%, afr) (gnomAD).

What do computational predictors say about COL4A4 p.Pro263Arg (c.788C>G)?

AlphaMissense predicts likely benign (score 0.1297) — an in-silico prediction, not a clinical call.

COL4A4 p.Pro263Arg

c.788C>G · rs369108674 · VCV930186

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1297 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

glomerulonephritis

Computational evidence

Protein change
AlphaMissense	0.1297	likely benign
REVEL	0.614	indeterminate
SaProt	LLR -6.35	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 9.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 140 kb · p 1.4e-05 · 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 0.0187% African / African-American · 14/74,822 alleles

Filtering AF 0.0112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00906%

Overall 0.00192% 31/1,613,424 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0187%	5,344
East Asian	0.00223%	44,870
Admixed American	0.00167%	59,974
Remaining individualsnot grpmax-eligible	0.0016%	62,476
European (non-Finnish)	0.00119%	84,279

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: COL4A4
Protein: p.Pro263Arg
Coding: c.788C>G
MANE Select: NM_000092
dbSNP: rs369108674
Type: single nucleotide variant
Location: chr2:227104000 (GRCh38)
Gene constraint: LOEUF 0.607 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 49.03 · 2 PDB
Residue 263: the 'triple-helical region' region

Full COL4A4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

glomerulonephritis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

COL4A4 p.Pro263fs Likely pathogenic ★ same residue
COL4A4 p.Gly285Glu Conflicting classifications of pathogenicity ★ ⚠ same condition
COL4A4 p.Pro416Ala Conflicting classifications of pathogenicity ★ ⚠ same condition
COL4A4 c.1030-2A>C Likely pathogenic ★★ same type
COL4A4 c.1099+1G>A Pathogenic ★★ same type
COL4A4 c.1099+1G>T Pathogenic/Likely pathogenic ★★ same type
COL4A4 c.1369+1G>A Pathogenic/Likely pathogenic ★★ same type
COL4A4 c.1370-2A>C 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/col4a4-p-pro263arg (accessed [today's date]).

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