Is COL4A6 p.Ala47= (c.141G>A) pathogenic?

COL4A6 p.Ala47= (c.141G>A) is classified Likely benign in COL4A6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-30). Very rare (popmax 0.000785%, nfe).

How common is COL4A6 p.Ala47= (c.141G>A) in the general population?

COL4A6 p.Ala47= (c.141G>A) is very rare (popmax 0.000785%, nfe) (gnomAD).

COL4A6 p.Ala47=

c.141G>A · rs2038741608 · VCV2997518

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000785%, nfe)

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 -4.6	GERP -3.7
Overall
CADD	0.506	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000785% European (non-Finnish) · 7/891,948 alleles

Filtering AF 0.000326% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00021%

Overall 0.00064% 7/1,093,825 alleles · very rare

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.Ala47=
Coding: c.141G>A
MANE Select: NM_033641
dbSNP: rs2038741608
Type: single nucleotide variant
Location: chrX:108310751 (GRCh38)
Structure: AlphaFold pLDDT 48.27
Residue 47: the 'triple-helical region' region

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

Similar variants

COL4A6 p.Ala47Glu Uncertain significance ★ ⚠ same residue
COL4A6 p.Ala47Val Uncertain significance ★ ⚠ same residue
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

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-ala47 (accessed [today's date]).

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