Is COL4A1 p.Pro602Ser (c.1804C>T) pathogenic?

COL4A1 p.Pro602Ser (c.1804C>T) is classified Conflicting classifications of pathogenicity in COL4A1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-10-24). AlphaMissense: likely benign (0.0841); Very rare (popmax 0.00801%, afr); Associated with Inborn genetic diseases.

What condition is associated with COL4A1 p.Pro602Ser (c.1804C>T)?

COL4A1 p.Pro602Ser (c.1804C>T) is associated with Inborn genetic diseases (ClinVar).

How common is COL4A1 p.Pro602Ser (c.1804C>T) in the general population?

COL4A1 p.Pro602Ser (c.1804C>T) is very rare (popmax 0.00801%, afr) (gnomAD).

What do computational predictors say about COL4A1 p.Pro602Ser (c.1804C>T)?

AlphaMissense predicts likely benign (score 0.0841) — an in-silico prediction, not a clinical call.

COL4A1 p.Pro602Ser

c.1804C>T · rs769247289 · VCV1519344

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0841 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0841	likely benign
REVEL	0.336	indeterminate
SaProt	LLR -8.70	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 9.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 30 kb · p 1.5e-10 · regional, not allelic
Overall
CADD	22.3	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 0.00801% African / African-American · 6/74,900 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.000868% 14/1,613,734 alleles · very rare exomes 11/1,461,554 · genomes 3/152,180 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,483
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,584
Admixed American	0.00333%	29,995
South Asian	0.00329%	30,362
East Asian	0.00223%	44,880
European (non-Finnish)	8.47e-05%	1,179,956

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: COL4A1
Protein: p.Pro602Ser
Coding: c.1804C>T
MANE Select: NM_001845
dbSNP: rs769247289
Type: single nucleotide variant
Location: chr13:110186478 (GRCh38)
Gene constraint: LOEUF 0.238 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 49.43 · 4 PDB
Residue 602: a modified residue (3-hydroxyproline); the 'triple-helical region' region; the 'disordered' region

Full COL4A1 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

COL4A1 p.Pro602Thr Uncertain significance ★ ⚠ same residue
COL4A1 p.Gly1580Ser Pathogenic ★★ same condition
COL4A1 p.Gly755Arg Pathogenic ★★ same condition
COL4A1 p.Ala1628Thr Uncertain significance ★★ ⚠ same condition
COL4A1 p.Ala683Thr Uncertain significance ★★ ⚠ same condition
COL4A1 p.Ala806Val Uncertain significance ★★ ⚠ same condition
COL4A1 p.Arg1495His Uncertain significance ★★ ⚠ same condition
COL4A1 p.Arg1668Lys 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/col4a1-p-pro602ser (accessed [today's date]).

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