Is COL4A2 p.Pro844Ser (c.2530C>T) pathogenic?

COL4A2 p.Pro844Ser (c.2530C>T) is classified Conflicting classifications of pathogenicity in COL4A2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-09-15). AlphaMissense: likely benign (0.1441); Ultra-rare (popmax 0.0135%, amr); Associated with Inborn genetic diseases.

What condition is associated with COL4A2 p.Pro844Ser (c.2530C>T)?

COL4A2 p.Pro844Ser (c.2530C>T) is associated with Inborn genetic diseases (ClinVar).

How common is COL4A2 p.Pro844Ser (c.2530C>T) in the general population?

COL4A2 p.Pro844Ser (c.2530C>T) is ultra-rare (popmax 0.0135%, amr) (gnomAD).

What do computational predictors say about COL4A2 p.Pro844Ser (c.2530C>T)?

AlphaMissense predicts likely benign (score 0.1441) — an in-silico prediction, not a clinical call.

COL4A2 p.Pro844Ser

c.2530C>T · rs763705148 · VCV421778

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1441 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0135%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1441	likely benign
REVEL	0.499	indeterminate
SaProt	LLR -9.09	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 5.8	GERP 0.24, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 62 kb · p 6e-16 · regional, not allelic
Overall
CADD	24.1	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 0.0135% Admixed American · 8/59,390 alleles

Filtering AF 0.00667% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00487%

Overall 0.000561% 9/1,603,094 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0135%	7,424
South Asian	0.00111%	89,798

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.Pro844Ser
Coding: c.2530C>T
MANE Select: NM_001846
dbSNP: rs763705148
Type: single nucleotide variant
Location: chr13:110478107 (GRCh38)
Gene constraint: LOEUF 0.618 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 47.97 · 4 PDB
Residue 844: the 'triple-helical region' region; the 'disordered' region

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.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
COL4A2 p.Arg1651His 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-pro844ser (accessed [today's date]).

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