Is COL4A2 p.Pro132Arg (c.395C>G) pathogenic?

COL4A2 p.Pro132Arg (c.395C>G) is classified Uncertain significance in COL4A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-21). AlphaMissense: likely benign (0.1339); Very rare (popmax 0.000171%, nfe); Associated with COL4A2-related disorder.

What condition is associated with COL4A2 p.Pro132Arg (c.395C>G)?

COL4A2 p.Pro132Arg (c.395C>G) is associated with COL4A2-related disorder (ClinVar).

How common is COL4A2 p.Pro132Arg (c.395C>G) in the general population?

COL4A2 p.Pro132Arg (c.395C>G) is very rare (popmax 0.000171%, nfe) (gnomAD).

What do computational predictors say about COL4A2 p.Pro132Arg (c.395C>G)?

AlphaMissense predicts likely benign (score 0.1339) — an in-silico prediction, not a clinical call.

COL4A2 p.Pro132Arg

c.395C>G · rs199561972 · VCV2628654

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1339 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000171%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

COL4A2-related disorder

Computational evidence

Protein change
AlphaMissense	0.1339	likely benign
REVEL	0.55	indeterminate
SaProt	LLR -8.45	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.4, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 143 kb · p 0.24 · regional, not allelic
Overall
CADD	23.3	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000171% European (non-Finnish) · 2/1,169,846 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000126% 2/1,585,174 alleles · very rare exomes 2/1,432,858 · genomes 0/152,316 · joint denominator

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: COL4A2
Protein: p.Pro132Arg
Coding: c.395C>G
MANE Select: NM_001846
dbSNP: rs199561972
Type: single nucleotide variant
Location: chr13:110428501 (GRCh38)
Gene constraint: LOEUF 0.618 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 47.97 · 4 PDB
Residue 132: the 'disordered' region

Full COL4A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

COL4A2-related disorder

Similar variants

COL4A2 p.Pro132Leu Benign/Likely benign ★★ ⚠ same residue
COL4A2 p.Gly1389Arg Pathogenic/Likely pathogenic ★★ same condition
COL4A2 p.Arg1069Gln Uncertain significance ★★ ⚠ same condition
COL4A2 p.Gly1622Arg Uncertain significance ★★ ⚠ same condition
COL4A2 p.Glu92Ter Likely pathogenic ★ same condition
COL4A2 p.Gly539Ser Likely pathogenic ★ ⚠ same condition
COL4A2 p.Gly872Arg Likely pathogenic ★ same condition
COL4A2 c.1776+1G>A Conflicting classifications of pathogenicity ★ 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/col4a2-p-pro132arg (accessed [today's date]).

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