Is COL4A5 p.Pro773Ser (c.2317C>T) pathogenic?

COL4A5 p.Pro773Ser (c.2317C>T) is classified Uncertain significance in COL4A5 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-24). AlphaMissense: likely benign (0.0863); Ultra-rare (popmax 0.0105%, afr); Associated with COL4A5-related disorder.

What condition is associated with COL4A5 p.Pro773Ser (c.2317C>T)?

COL4A5 p.Pro773Ser (c.2317C>T) is associated with COL4A5-related disorder (ClinVar).

How common is COL4A5 p.Pro773Ser (c.2317C>T) in the general population?

COL4A5 p.Pro773Ser (c.2317C>T) is ultra-rare (popmax 0.0105%, afr) (gnomAD).

What do computational predictors say about COL4A5 p.Pro773Ser (c.2317C>T)?

AlphaMissense predicts likely benign (score 0.0863) — an in-silico prediction, not a clinical call.

COL4A5 p.Pro773Ser

c.2317C>T · rs755499934 · VCV2521060

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0863 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0105%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

COL4A5-related disorder

Computational evidence

Protein change
AlphaMissense	0.0863	likely benign
REVEL	0.594	indeterminate
SaProt	LLR -7.52	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 3.2	GERP 1.7, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 256 kb · p 6e-09 · regional, not allelic
Overall
CADD	19.65	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0105% African / African-American · 6/57,098 alleles

Filtering AF 0.00456% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00408%

Overall 0.0048% 58/1,209,518 alleles · ultra-rare exomes 52/1,097,821 · genomes 6/111,697 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0105%	9,516
European (non-Finnish)	0.00581%	17,209

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.Pro773Ser
Coding: c.2317C>T
MANE Select: NM_033380
dbSNP: rs755499934
Type: single nucleotide variant
Location: chrX:108606814 (GRCh38)
Structure: AlphaFold pLDDT 49.04 · 2 PDB
Residue 773: the 'triple-helical region' region; the 'disordered' region

Full COL4A5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

COL4A5-related disorder

Similar variants

COL4A5 c.1779+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL4A5 c.1780-1G>T Pathogenic ★★ same condition
COL4A5 c.2146+1G>T Pathogenic/Likely pathogenic ★★ same condition
COL4A5 c.2147-2A>G Pathogenic/Likely pathogenic ★★ same condition
COL4A5 c.2244+1G>T Pathogenic/Likely pathogenic ★★ same condition
COL4A5 c.3016+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL4A5 c.321+1G>A Likely pathogenic ★★ same condition
COL4A5 c.385-2A>G Pathogenic/Likely pathogenic ★★ 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-pro773ser (accessed [today's date]).

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