Is COL4A6 p.Ala976= (c.2928C>T) pathogenic?

COL4A6 p.Ala976= (c.2928C>T) is classified Likely benign in COL4A6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-15). Very rare (popmax 0.00354%, afr).

How common is COL4A6 p.Ala976= (c.2928C>T) in the general population?

COL4A6 p.Ala976= (c.2928C>T) is very rare (popmax 0.00354%, afr) (gnomAD).

COL4A6 p.Ala976=

c.2928C>T · rs1486466984 · VCV2725870

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00354%, 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 0.35	GERP -2.9, phastCons 0.76
Overall
CADD	0.723	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00354% African / African-American · 2/56,485 alleles

Filtering AF 0.000587% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000414%

Overall 0.00108% 13/1,199,112 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00354%	28,243
South Asian	0.00183%	54,784
European (non-Finnish)	0.00112%	88,998

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.Ala976=
Coding: c.2928C>T
MANE Select: NM_033641
dbSNP: rs1486466984
Type: single nucleotide variant
Location: chrX:108175118 (GRCh38)
Structure: AlphaFold pLDDT 48.27
Residue 976: 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-ala976 (accessed [today's date]).

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