Is COL4A6 p.Pro383Ser (c.1147C>T) pathogenic?

COL4A6 p.Pro383Ser (c.1147C>T) is classified Uncertain significance in COL4A6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-03). AlphaMissense: likely benign (0.0752); Very rare (popmax 0.00174%, afr); Associated with COL4A6-related disorder.

What condition is associated with COL4A6 p.Pro383Ser (c.1147C>T)?

COL4A6 p.Pro383Ser (c.1147C>T) is associated with COL4A6-related disorder (ClinVar).

How common is COL4A6 p.Pro383Ser (c.1147C>T) in the general population?

COL4A6 p.Pro383Ser (c.1147C>T) is very rare (popmax 0.00174%, afr) (gnomAD).

What do computational predictors say about COL4A6 p.Pro383Ser (c.1147C>T)?

AlphaMissense predicts likely benign (score 0.0752) — an in-silico prediction, not a clinical call.

COL4A6 p.Pro383Ser

c.1147C>T · rs2035080047 · VCV2628765

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0752 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00174%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

COL4A6-related disorder

Computational evidence

Protein change
AlphaMissense	0.0752	likely benign
REVEL	0.248	benign-leaning
SaProt	LLR -8.03	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP -0.58, phastCons 0.99
Regional constraint	o/e 0.96	unconstrained · MANE · 281 kb · p 0.15 · regional, not allelic
Overall
CADD	4.935	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P384S vs ClinVar P383S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00174% African / African-American · 1/57,308 alleles

Filtering AF 3.7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.4e-05%

Overall 0.000248% 3/1,207,690 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00174%	57,308
European (non-Finnish)	0.000224%	446,899

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.Pro383Ser
Coding: c.1147C>T
MANE Select: NM_033641
dbSNP: rs2035080047
Type: single nucleotide variant
Location: chrX:108192506 (GRCh38)
Structure: AlphaFold pLDDT 48.27
Residue 383: the 'triple-helical region' 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.Ser1420Thr Uncertain significance ★ ⚠ same condition
COL4A6 p.Arg517Gln Uncertain significance ⚠ same condition
COL4A6 p.Ile356Val Uncertain significance ⚠ same condition
COL4A6 p.Pro1280Thr 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-pro383ser (accessed [today's date]).

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