Is COL4A5 p.Pro797Ser (c.2389C>T) pathogenic?

COL4A5 p.Pro797Ser (c.2389C>T) is classified Conflicting classifications of pathogenicity in COL4A5 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-08-29). AlphaMissense: likely benign (0.0815); Ultra-rare (popmax 0.0246%, sas); Associated with Inborn genetic diseases.

What condition is associated with COL4A5 p.Pro797Ser (c.2389C>T)?

COL4A5 p.Pro797Ser (c.2389C>T) is associated with Inborn genetic diseases (ClinVar).

How common is COL4A5 p.Pro797Ser (c.2389C>T) in the general population?

COL4A5 p.Pro797Ser (c.2389C>T) is ultra-rare (popmax 0.0246%, sas) (gnomAD).

What do computational predictors say about COL4A5 p.Pro797Ser (c.2389C>T)?

AlphaMissense predicts likely benign (score 0.0815) — an in-silico prediction, not a clinical call.

COL4A5 p.Pro797Ser

c.2389C>T · rs1409239477 · VCV2150640

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0815 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0246%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0815	likely benign
REVEL	0.3	indeterminate
SaProt	LLR -8.27	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 0.17, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 256 kb · p 6e-09 · regional, not allelic
Overall
CADD	14.12	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 0.0246% South Asian · 14/56,955 alleles

Filtering AF 0.0148% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0119%

Overall 0.00132% 16/1,210,818 alleles · ultra-rare exomes 16/1,097,559 · genomes 0/113,259 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0246%	4,068
Remaining individualsnot grpmax-eligible	0.0021%	47,628
European (non-Finnish)	0.000112%	894,871

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: COL4A5
Protein: p.Pro797Ser
Coding: c.2389C>T
MANE Select: NM_033380
dbSNP: rs1409239477
Type: single nucleotide variant
Location: chrX:108606886 (GRCh38)
Structure: AlphaFold pLDDT 49.04 · 2 PDB
Residue 797: the 'triple-helical region' region; the 'disordered' region

Full COL4A5 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

COL4A5 c.546+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL4A5 p.Gly135Val Likely pathogenic ★★ same condition
COL4A5 p.Gly426Arg Pathogenic/Likely pathogenic ★★ same condition
COL4A5 p.Arg1319Trp Uncertain significance ★★ ⚠ same condition
COL4A5 p.Arg1518His Uncertain significance ★★ ⚠ same condition
COL4A5 p.Arg1631His Uncertain significance ★★ ⚠ same condition
COL4A5 p.Arg862Gly Uncertain significance ★★ ⚠ same condition
COL4A5 p.Gly1153Arg 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/col4a5-p-pro797ser (accessed [today's date]).

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