Is COL4A4 p.Pro1029Ser (c.3085C>T) pathogenic?

COL4A4 p.Pro1029Ser (c.3085C>T) is classified Conflicting classifications of pathogenicity in COL4A4 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-19). AlphaMissense: likely benign (0.0866); Ultra-rare (popmax 0.02%, eas); Associated with Inborn genetic diseases.

What condition is associated with COL4A4 p.Pro1029Ser (c.3085C>T)?

COL4A4 p.Pro1029Ser (c.3085C>T) is associated with Inborn genetic diseases (ClinVar).

How common is COL4A4 p.Pro1029Ser (c.3085C>T) in the general population?

COL4A4 p.Pro1029Ser (c.3085C>T) is ultra-rare (popmax 0.02%, eas) (gnomAD).

What do computational predictors say about COL4A4 p.Pro1029Ser (c.3085C>T)?

AlphaMissense predicts likely benign (score 0.0866) — an in-silico prediction, not a clinical call.

COL4A4 p.Pro1029Ser

c.3085C>T · rs760539669 · VCV2143660

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0866 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0866	likely benign
REVEL	0.458	indeterminate
SaProt	LLR -9.06	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 4.5	GERP 2, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 140 kb · p 1.4e-05 · regional, not allelic
Overall
CADD	19.41	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 0.02% East Asian · 9/44,896 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00779%

Overall 0.000682% 11/1,614,058 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.02%	4,988
Remaining individualsnot grpmax-eligible	0.0032%	31,244

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: COL4A4
Protein: p.Pro1029Ser
Coding: c.3085C>T
MANE Select: NM_000092
dbSNP: rs760539669
Type: single nucleotide variant
Location: chr2:227051042 (GRCh38)
Gene constraint: LOEUF 0.607 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 49.03 · 2 PDB
Residue 1029: the 'triple-helical region' region; the 'disordered' region

Full COL4A4 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

COL4A4 p.Arg349Ter Pathogenic/Likely pathogenic ★★ same condition
COL4A4 p.Cys1588Ser Likely pathogenic ★★ same condition
COL4A4 p.Pro1029fs Likely pathogenic ★★ same residue
COL4A4 c.4522+6G>A Uncertain significance ★★ same condition
COL4A4 p.Ala1546Thr Uncertain significance ★★ ⚠ same condition
COL4A4 p.Arg1565Cys Uncertain significance ★★ ⚠ same condition
COL4A4 p.Arg641Gln Uncertain significance ★★ ⚠ same condition
COL4A4 p.Arg811Thr 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/col4a4-p-pro1029ser (accessed [today's date]).

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