Is COL4A4 p.Arg708= (c.2122A>C) pathogenic?

COL4A4 p.Arg708= (c.2122A>C) is classified Likely benign in COL4A4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-26). Absent from gnomAD v4.1.

How common is COL4A4 p.Arg708= (c.2122A>C) in the general population?

COL4A4 p.Arg708= (c.2122A>C) is absent from gnomAD v4.1 (gnomAD).

COL4A4 p.Arg708=

c.2122A>C · rs765570194 · VCV1155097

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.3	GERP -1.1, phastCons 0.91
Overall
CADD	6.208	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.Arg708=
Coding: c.2122A>C
MANE Select: NM_000092
dbSNP: rs765570194
Type: single nucleotide variant
Location: chr2:227060178 (GRCh38)
Gene constraint: LOEUF 0.607 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 49.03 · 2 PDB
Residue 708: 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.Arg708Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
COL4A4 p.Arg708Ser 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-arg708 (accessed [today's date]).

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