Is COL4A2 p.Pro442Ser (c.1324C>T) pathogenic?

COL4A2 p.Pro442Ser (c.1324C>T) is classified Benign in COL4A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-23). AlphaMissense: likely benign (0.0796); Ultra-rare (popmax 0.0883%, amr).

How common is COL4A2 p.Pro442Ser (c.1324C>T) in the general population?

COL4A2 p.Pro442Ser (c.1324C>T) is ultra-rare (popmax 0.0883%, amr) (gnomAD).

What do computational predictors say about COL4A2 p.Pro442Ser (c.1324C>T)?

AlphaMissense predicts likely benign (score 0.0796) — an in-silico prediction, not a clinical call.

COL4A2 p.Pro442Ser

c.1324C>T · rs764002137 · VCV1643085

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0796 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0883%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0796	likely benign
REVEL	0.253	benign-leaning
SaProt	LLR -8.71	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 1.9	GERP -0.95, phastCons 0.004
Regional constraint	o/e 0.95	unconstrained · MANE · 143 kb · p 0.24 · regional, not allelic
Overall
CADD	11.52	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0883% Admixed American · 53/60,002 alleles

Filtering AF 0.0693% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0626%

Overall 0.00359% 58/1,613,768 alleles · ultra-rare exomes 51/1,461,582 · genomes 7/152,186 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0883%	1,132
South Asian	0.00329%	30,359
Remaining individualsnot grpmax-eligible	0.0016%	62,470
European (non-Finnish)	8.47e-05%	1,179,966

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.Pro442Ser
Coding: c.1324C>T
MANE Select: NM_001846
dbSNP: rs764002137
Type: single nucleotide variant
Location: chr13:110450439 (GRCh38)
Gene constraint: LOEUF 0.618 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 47.97 · 4 PDB
Residue 442: 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 p.Pro442Gln Likely benign ★ same residue
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

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-pro442ser (accessed [today's date]).

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