Is COL4A6 p.Asp577= (c.1731C>T) pathogenic?

COL4A6 p.Asp577= (c.1731C>T) is classified Likely benign in COL4A6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-18). Ultra-rare (popmax 0.0369%, afr).

How common is COL4A6 p.Asp577= (c.1731C>T) in the general population?

COL4A6 p.Asp577= (c.1731C>T) is ultra-rare (popmax 0.0369%, afr) (gnomAD).

COL4A6 p.Asp577=

c.1731C>T · rs769251262 · VCV2739097

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0369%, 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 -0.38	GERP -2.3, phastCons 0.001
Overall
CADD	0.093	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0369% African / African-American · 21/56,870 alleles

Filtering AF 0.0247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0207%

Overall 0.00472% 57/1,207,313 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0369%	2,708
South Asian	0.00712%	14,051
Remaining individualsnot grpmax-eligible	0.00421%	23,771
European (non-Finnish)	0.00336%	29,798

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: COL4A6
Protein: p.Asp577=
Coding: c.1731C>T
MANE Select: NM_033641
dbSNP: rs769251262
Type: single nucleotide variant
Location: chrX:108187884 (GRCh38)
Structure: AlphaFold pLDDT 48.27
Residue 577: the 'triple-helical region' region; the 'disordered' region

Full COL4A6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COL4A6 c.3970+5G>A Uncertain significance ★★ same type
COL4A6 p.Ala1275Thr Uncertain significance ★★ ⚠ same type
COL4A6 p.Ala398Ser Uncertain significance ★★ ⚠ same type
COL4A6 p.Ala421Gly Uncertain significance ★★ ⚠ same type
COL4A6 p.Ala748Val Uncertain significance ★★ ⚠ same type
COL4A6 p.Ala886Thr Uncertain significance ★★ ⚠ same type
COL4A6 p.Arg1025Trp Uncertain significance ★★ ⚠ same type
COL4A6 p.Arg1262Gln 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/col4a6-p-asp577 (accessed [today's date]).

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