Is COL4A2 p.Gly1663= (c.4989C>T) pathogenic?

COL4A2 p.Gly1663= (c.4989C>T) is classified Likely benign in COL4A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-06). Very rare (popmax 0.00167%, amr).

How common is COL4A2 p.Gly1663= (c.4989C>T) in the general population?

COL4A2 p.Gly1663= (c.4989C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

COL4A2 p.Gly1663=

c.4989C>T · rs759828986 · VCV1973501

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

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 -3.8
Overall
CADD	1.414	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,030 alleles

Overall 0.000186% 3/1,613,696 alleles · very rare exomes 1/1,461,370 · genomes 2/152,326 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,030
Remaining individualsnot grpmax-eligible	0.0016%	62,502
African / African-American	0.00133%	75,052

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: COL4A2
Protein: p.Gly1663=
Coding: c.4989C>T
MANE Select: NM_001846
dbSNP: rs759828986
Type: single nucleotide variant
Location: chr13:110512041 (GRCh38)
Gene constraint: LOEUF 0.618 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 47.97 · 4 PDB
Residue 1663: the collagen iv nc1 domain; a turn

Full COL4A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COL4A2 p.Gly1663Arg Uncertain significance ★ ⚠ same residue
COL4A2 p.Gly1663Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
COL4A2 c.361-1G>A Pathogenic/Likely pathogenic ★★ same type
COL4A2 p.Gly1389Arg Pathogenic/Likely pathogenic ★★ same type
COL4A2 p.Gly619Asp Likely pathogenic ★★ same type
COL4A2 c.2425+3G>A Uncertain significance ★★ same type
COL4A2 c.315+5G>A Uncertain significance ★★ same type
COL4A2 c.726+4A>G Uncertain significance ★★ 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/col4a2-p-gly1663 (accessed [today's date]).

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