Is COL4A2 p.Pro790Ala (c.2368C>G) pathogenic?

COL4A2 p.Pro790Ala (c.2368C>G) is classified Uncertain significance in COL4A2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-10). AlphaMissense: likely benign (0.0643); Absent from gnomAD v4.1.

How common is COL4A2 p.Pro790Ala (c.2368C>G) in the general population?

COL4A2 p.Pro790Ala (c.2368C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COL4A2 p.Pro790Ala (c.2368C>G)?

AlphaMissense predicts likely benign (score 0.0643) — an in-silico prediction, not a clinical call.

COL4A2 p.Pro790Ala

c.2368C>G · VCV3631590

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0643 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0643	likely benign
REVEL	0.523	indeterminate
SaProt	LLR -9.02	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.6, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 62 kb · p 6e-16 · regional, not allelic
Overall
CADD	24.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: COL4A2
Protein: p.Pro790Ala
Coding: c.2368C>G
MANE Select: NM_001846
Type: single nucleotide variant
Location: chr13:110473093 (GRCh38)
Gene constraint: LOEUF 0.618 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 47.97 · 4 PDB
Residue 790: the 'triple-helical region' region; the 'disordered' region

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

Similar variants

COL4A2 c.361-1G>A Pathogenic/Likely pathogenic ★★ same type
COL4A2 p.Gly1389Arg Pathogenic/Likely pathogenic ★★ same type
COL4A2 p.Gly619Asp Likely pathogenic ★★ same type
COL4A2 c.2425+3G>A Uncertain significance ★★ same type
COL4A2 c.315+5G>A Uncertain significance ★★ same type
COL4A2 c.726+4A>G Uncertain significance ★★ same type
COL4A2 p.Ala1183Val Uncertain significance ★★ ⚠ same type
COL4A2 p.Ala1363Val 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/col4a2-p-pro790ala (accessed [today's date]).

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