Is COL4A6 p.Ser1285= (c.3855G>A) pathogenic?

COL4A6 p.Ser1285= (c.3855G>A) is classified Benign/Likely benign in COL4A6 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-27). Common (popmax 10.5%, afr) — too common for a highly-penetrant pathogenic allele; Associated with hearing loss, X-linked 6.

What condition is associated with COL4A6 p.Ser1285= (c.3855G>A)?

COL4A6 p.Ser1285= (c.3855G>A) is associated with hearing loss, X-linked 6 (ClinVar).

COL4A6 p.Ser1285=

Q: How common is COL4A6 p.Ser1285= (c.3855G>A) in the general population?

COL4A6 p.Ser1285= (c.3855G>A) is common (popmax 10.5%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3855G>A · rs34132805 · VCV258277

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 10.5%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

hearing loss, X-linked 6

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 -5.2	GERP -2.1
Overall
CADD	0.797	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 10.5% African / African-American · 5,951/56,540 alleles

Filtering AF 10.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 10.2%

Overall 0.569% 6,879/1,208,093 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	10.5%	10
Admixed American	0.805%	124
Remaining individualsnot grpmax-eligible	0.765%	131
Middle Eastern	0.438%	228
South Asian	0.03%	3,329
European (non-Finnish)	0.0179%	5,591

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.Ser1285=
Coding: c.3855G>A
MANE Select: NM_033641
dbSNP: rs34132805
Type: single nucleotide variant
Location: chrX:108164992 (GRCh38)
Structure: AlphaFold pLDDT 48.27
Residue 1285: the 'triple-helical region' region; the 'disordered' region

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

Disease context

hearing loss, X-linked 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

COL4A6 p.Ser1285Leu Uncertain significance ★ ⚠ same residue
COL4A6 p.Arg1269Ter Uncertain significance ★★ same condition
COL4A6 p.Gly1484Arg Uncertain significance ★★ ⚠ same condition
COL4A6 c.2132-6G>A Benign/Likely benign ★★ same condition
COL4A6 c.2132-6G>T Benign/Likely benign ★★ same condition
COL4A6 c.2956+39G>A Benign ★★ same condition
COL4A6 c.3138+17C>T Benign/Likely benign ★★ same condition
COL4A6 c.3139-4G>A Benign/Likely benign ★★ 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-ser1285 (accessed [today's date]).

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