Is COL4A5 p.Ile703Val (c.2107A>G) pathogenic?

COL4A5 p.Ile703Val (c.2107A>G) is classified Benign in COL4A5 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-05-28). AlphaMissense: likely benign (0.1018); Ultra-rare (popmax 0.0125%, eas); Associated with X-linked Alport syndrome.

What condition is associated with COL4A5 p.Ile703Val (c.2107A>G)?

COL4A5 p.Ile703Val (c.2107A>G) is associated with X-linked Alport syndrome (ClinVar).

How common is COL4A5 p.Ile703Val (c.2107A>G) in the general population?

COL4A5 p.Ile703Val (c.2107A>G) is ultra-rare (popmax 0.0125%, eas) (gnomAD).

How is Alport syndrome inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about COL4A5 p.Ile703Val (c.2107A>G)?

AlphaMissense predicts likely benign (score 0.1018) — an in-silico prediction, not a clinical call.

COL4A5 p.Ile703Val

c.2107A>G · rs104886155 · VCV24486

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1018 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0125%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

X-linked Alport syndrome

Computational evidence

Protein change
AlphaMissense	0.1018	likely benign
REVEL	0.532	indeterminate
SaProt	LLR -7.51	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 2	GERP 0.73, phastCons 0.98
Regional constraint	o/e 0.84	unconstrained · MANE · 256 kb · p 6e-09 · regional, not allelic
Overall
CADD	12.03	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 0.0125% East Asian · 4/32,104 alleles

Filtering AF 0.0042% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.000344% 4/1,164,476 alleles · ultra-rare exomes 4/1,050,529 · genomes 0/113,947 · joint denominator

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.Ile703Val
Coding: c.2107A>G
MANE Select: NM_033380
dbSNP: rs104886155
Type: single nucleotide variant
Location: chrX:108601950 (GRCh38)
Structure: AlphaFold pLDDT 49.04 · 2 PDB
Residue 703: the 'triple-helical region' region; the 'disordered' region

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

Disease context

X-linked Alport syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Alport syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked dominant
Onset: Adolescent, Adult, Childhood, Elderly

Similar variants

COL4A5 p.Ile703= Likely benign ★ same residue
COL4A5 c.1033-1G>A Pathogenic ★★ same condition
COL4A5 c.1033-2A>G Pathogenic/Likely pathogenic ★★ same condition
COL4A5 c.1339+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL4A5 c.141+1G>A Pathogenic ★★ same condition
COL4A5 c.1424-20T>A Pathogenic/Likely pathogenic ★★ same condition
COL4A5 c.1516+1G>C Pathogenic ★★ same condition
COL4A5 c.1780-1G>T 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-ile703val (accessed [today's date]).

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