Is COL4A2 p.Ser30Arg (c.90C>A) pathogenic?

COL4A2 p.Ser30Arg (c.90C>A) is classified Uncertain significance in COL4A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-24). AlphaMissense: likely benign (0.265); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with COL4A2 p.Ser30Arg (c.90C>A)?

COL4A2 p.Ser30Arg (c.90C>A) is associated with Inborn genetic diseases (ClinVar).

How common is COL4A2 p.Ser30Arg (c.90C>A) in the general population?

COL4A2 p.Ser30Arg (c.90C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COL4A2 p.Ser30Arg (c.90C>A)?

AlphaMissense predicts likely benign (score 0.265) — an in-silico prediction, not a clinical call.

COL4A2 p.Ser30Arg

c.90C>A · VCV3495488

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.265 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.265	likely benign
REVEL	0.202	benign-leaning
SaProt	LLR -7.66	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 1.6	GERP 0.3, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 143 kb · p 0.24 · regional, not allelic
Overall
CADD	21.1	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.Ser30Arg
Coding: c.90C>A
MANE Select: NM_001846
Type: single nucleotide variant
Location: chr13:110308114 (GRCh38)
Gene constraint: LOEUF 0.618 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 47.97 · 4 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

COL4A2 p.Ser30Asn Uncertain significance ★ ⚠ same residue
COL4A2 p.Arg1193Cys Uncertain significance ★★ ⚠ same condition
COL4A2 p.Arg1336Lys Uncertain significance ★★ ⚠ same condition
COL4A2 p.Arg1452Trp Uncertain significance ★★ ⚠ same condition
COL4A2 p.Arg1540Trp Uncertain significance ★★ ⚠ same condition
COL4A2 p.Arg1560Gln Uncertain significance ★★ ⚠ same condition
COL4A2 p.Arg1589His Uncertain significance ★★ ⚠ same condition
COL4A2 p.Arg1617Gln 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/col4a2-p-ser30arg (accessed [today's date]).

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