Is COL4A2 p.Pro330Ser (c.988C>T) pathogenic?

COL4A2 p.Pro330Ser (c.988C>T) is classified Uncertain significance in COL4A2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-08-11). AlphaMissense: likely benign (0.0697); Very rare (popmax 0.00136%, nfe).

How common is COL4A2 p.Pro330Ser (c.988C>T) in the general population?

COL4A2 p.Pro330Ser (c.988C>T) is very rare (popmax 0.00136%, nfe) (gnomAD).

What do computational predictors say about COL4A2 p.Pro330Ser (c.988C>T)?

AlphaMissense predicts likely benign (score 0.0697) — an in-silico prediction, not a clinical call.

COL4A2 p.Pro330Ser

c.988C>T · rs1256447856 · VCV1802140

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0697 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00136%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0697	likely benign
REVEL	0.229	benign-leaning
SaProt	LLR -7.89	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 -0.42	GERP -2.5
Regional constraint	o/e 0.95	unconstrained · MANE · 143 kb · p 0.24 · regional, not allelic
Overall
CADD	6.764	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 0.00136% European (non-Finnish) · 16/1,180,018 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00105% 17/1,614,108 alleles · very rare exomes 17/1,461,876 · genomes 0/152,232 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00136%	73,751
African / African-American	0.00133%	75,024

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.Pro330Ser
Coding: c.988C>T
MANE Select: NM_001846
dbSNP: rs1256447856
Type: single nucleotide variant
Location: chr13:110445859 (GRCh38)
Gene constraint: LOEUF 0.618 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 47.97 · 4 PDB
Residue 330: 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-pro330ser (accessed [today's date]).

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