Is COL4A5 p.Ala754Ser (c.2260G>T) pathogenic?

COL4A5 p.Ala754Ser (c.2260G>T) is classified Uncertain significance in COL4A5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-07). AlphaMissense: likely benign (0.0753); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with COL4A5 p.Ala754Ser (c.2260G>T)?

COL4A5 p.Ala754Ser (c.2260G>T) is associated with Inborn genetic diseases (ClinVar).

How common is COL4A5 p.Ala754Ser (c.2260G>T) in the general population?

COL4A5 p.Ala754Ser (c.2260G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COL4A5 p.Ala754Ser (c.2260G>T)?

AlphaMissense predicts likely benign (score 0.0753) — an in-silico prediction, not a clinical call.

COL4A5 p.Ala754Ser

c.2260G>T · rs2524346316 · VCV2482067

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0753 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0753	likely benign
REVEL	0.301	indeterminate
SaProt	LLR -4.98	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 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 256 kb · p 6e-09 · regional, not allelic
Overall
CADD	23.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: COL4A5
Protein: p.Ala754Ser
Coding: c.2260G>T
MANE Select: NM_033380
dbSNP: rs2524346316
Type: single nucleotide variant
Location: chrX:108606757 (GRCh38)
Structure: AlphaFold pLDDT 49.04 · 2 PDB
Residue 754: 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 p.Ala754= Likely benign ★ same residue
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

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-ala754ser (accessed [today's date]).

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