Is COL4A2 p.Pro149Ala (c.445C>G) pathogenic?

COL4A2 p.Pro149Ala (c.445C>G) is classified Benign in COL4A2 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-06-25). AlphaMissense: likely benign (0.0654); Rare (popmax 0.107%, sas).

How common is COL4A2 p.Pro149Ala (c.445C>G) in the general population?

COL4A2 p.Pro149Ala (c.445C>G) is rare (popmax 0.107%, sas) (gnomAD).

What do computational predictors say about COL4A2 p.Pro149Ala (c.445C>G)?

AlphaMissense predicts likely benign (score 0.0654) — an in-silico prediction, not a clinical call.

COL4A2 p.Pro149Ala

c.445C>G · rs548601003 · VCV1558748

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0654 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.107%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0654	likely benign
REVEL	0.22	benign-leaning
SaProt	LLR -8.26	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.51	GERP -2.2
Regional constraint	o/e 0.95	unconstrained · MANE · 143 kb · p 0.24 · regional, not allelic
Overall
CADD	10.62	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 0.107% South Asian · 92/85,832 alleles

Filtering AF 0.0895% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0829%

Overall 0.0063% 99/1,572,342 alleles · rare exomes 91/1,420,066 · genomes 8/152,276 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.107%	933
Remaining individualsnot grpmax-eligible	0.00822%	12,162
African / African-American	0.00139%	71,758
European (non-Finnish)	8.59e-05%	1,163,556

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.Pro149Ala
Coding: c.445C>G
MANE Select: NM_001846
dbSNP: rs548601003
Type: single nucleotide variant
Location: chr13:110428551 (GRCh38)
Gene constraint: LOEUF 0.618 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 47.97 · 4 PDB
Residue 149: the 'disordered' region

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

Similar variants

COL4A2 p.Pro149His Uncertain significance ★ ⚠ 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-pro149ala (accessed [today's date]).

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