Is COL4A4 p.Pro995= (c.2985C>G) pathogenic?

COL4A4 p.Pro995= (c.2985C>G) is classified Likely benign in COL4A4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-29). Absent from gnomAD v4.1.

How common is COL4A4 p.Pro995= (c.2985C>G) in the general population?

COL4A4 p.Pro995= (c.2985C>G) is absent from gnomAD v4.1 (gnomAD).

COL4A4 p.Pro995=

c.2985C>G · rs79261248 · VCV2113118

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -3.5	GERP -3.3
Overall
CADD	0.031	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: COL4A4
Protein: p.Pro995=
Coding: c.2985C>G
MANE Select: NM_000092
dbSNP: rs79261248
Type: single nucleotide variant
Location: chr2:227051142 (GRCh38)
Gene constraint: LOEUF 0.607 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 49.03 · 2 PDB
Residue 995: 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.Pro995Arg Uncertain significance ★ ⚠ same residue
COL4A4 p.Pro995Ser Uncertain significance ★ ⚠ 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
COL4A4 c.1370-2A>C Likely pathogenic ★★ same type
COL4A4 c.1459+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/col4a4-p-pro995 (accessed [today's date]).

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