Is COL4A4 p.Pro883= (c.2649C>T) pathogenic?

COL4A4 p.Pro883= (c.2649C>T) is classified Likely benign in COL4A4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-17). Very rare (popmax 0.00801%, afr).

How common is COL4A4 p.Pro883= (c.2649C>T) in the general population?

COL4A4 p.Pro883= (c.2649C>T) is very rare (popmax 0.00801%, afr) (gnomAD).

COL4A4 p.Pro883=

c.2649C>T · rs1318425498 · VCV1658700

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.21	GERP -1, phastCons 0.001
Overall
CADD	1.292	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00801% African / African-American · 6/74,880 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.000682% 11/1,613,864 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,480
South Asian	0.0011%	91,072
European (non-Finnish)	0.000339%	294,989

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.Pro883=
Coding: c.2649C>T
MANE Select: NM_000092
dbSNP: rs1318425498
Type: single nucleotide variant
Location: chr2:227056012 (GRCh38)
Gene constraint: LOEUF 0.607 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 49.03 · 2 PDB
Residue 883: the 'triple-helical region' region; the 'disordered' region

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

Similar variants

COL4A4 p.Pro883Ala Uncertain significance ★ ⚠ same residue
COL4A4 p.Pro883Leu Uncertain significance ★ ⚠ same residue
COL4A4 p.Pro883Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
COL4A4 p.Pro883Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-pro883 (accessed [today's date]).

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