Is COL4A6 p.Pro436= (c.1308A>C) pathogenic?

COL4A6 p.Pro436= (c.1308A>C) is classified Likely benign in COL4A6 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-07-15). Rare (popmax 0.208%, mid); Associated with COL4A6-related disorder.

What condition is associated with COL4A6 p.Pro436= (c.1308A>C)?

COL4A6 p.Pro436= (c.1308A>C) is associated with COL4A6-related disorder (ClinVar).

How common is COL4A6 p.Pro436= (c.1308A>C) in the general population?

COL4A6 p.Pro436= (c.1308A>C) is rare (popmax 0.208%, mid) (gnomAD).

COL4A6 p.Pro436=

c.1308A>C · rs865851476 · VCV3035687

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.208%, mid)

Conditions

COL4A6-related disorder

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 -0.096	GERP -2.5, phastCons 0.14
Overall
CADD	6.01	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.208% Middle Eastern · 9/4,335 alleles

Filtering AF 0.108% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0808%

Overall 0.00182% 20/1,096,612 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.208%	482
African / African-American	0.00346%	28,862
Remaining individualsnot grpmax-eligible	0.0021%	47,581
South Asian	0.00177%	56,561
European (non-Finnish)	0.000782%	127,832

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.Pro436=
Coding: c.1308A>C
MANE Select: NM_033641
dbSNP: rs865851476
Type: single nucleotide variant
Location: chrX:108191406 (GRCh38)
Structure: AlphaFold pLDDT 48.27
Residue 436: the 'triple-helical region' region; the 'disordered' region

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

Disease context

COL4A6-related disorder

Similar variants

COL4A6 p.Glu453Asp Uncertain significance ★★ ⚠ same condition
COL4A6 p.Val1555Ile Uncertain significance ★★ ⚠ same condition
COL4A6 p.Ala1548Thr Conflicting classifications of pathogenicity ★ ⚠ same condition
COL4A6 p.Ile1152Thr Conflicting classifications of pathogenicity ★ ⚠ same condition
COL4A6 p.Pro383Ser Uncertain significance ★ ⚠ same condition
COL4A6 p.Ser1420Thr Uncertain significance ★ ⚠ same condition
COL4A6 p.Arg517Gln Uncertain significance ⚠ same condition
COL4A6 p.Ile356Val Uncertain significance ⚠ same condition

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-pro436 (accessed [today's date]).

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