Is COL4A2 p.Pro568Ser (c.1702C>T) pathogenic?

COL4A2 p.Pro568Ser (c.1702C>T) is classified Uncertain significance in COL4A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-03-09). AlphaMissense: likely benign (0.0784); Very rare (popmax 8.47e-05%, nfe); Associated with intellectual disability.

What condition is associated with COL4A2 p.Pro568Ser (c.1702C>T)?

COL4A2 p.Pro568Ser (c.1702C>T) is associated with intellectual disability (ClinVar).

How common is COL4A2 p.Pro568Ser (c.1702C>T) in the general population?

COL4A2 p.Pro568Ser (c.1702C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about COL4A2 p.Pro568Ser (c.1702C>T)?

AlphaMissense predicts likely benign (score 0.0784) — an in-silico prediction, not a clinical call.

COL4A2 p.Pro568Ser

c.1702C>T · VCV4074791

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0784 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability

Computational evidence

Protein change
AlphaMissense	0.0784	likely benign
REVEL	0.235	benign-leaning
SaProt	LLR -9.04	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.4, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 62 kb · p 6e-16 · regional, not allelic
Overall
CADD	19.95	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 8.47e-05% European (non-Finnish) · 1/1,180,050 alleles

Overall 6.19e-05% 1/1,614,220 alleles · very rare exomes 1/1,461,852 · genomes 0/152,368 · 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: COL4A2
Protein: p.Pro568Ser
Coding: c.1702C>T
MANE Select: NM_001846
Type: single nucleotide variant
Location: chr13:110462310 (GRCh38)
Gene constraint: LOEUF 0.618 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 47.97 · 4 PDB
Residue 568: the 'triple-helical region' region; the 'disordered' region

Full COL4A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

COL4A2 p.Pro568= Likely benign ★ same residue
COL4A2 p.Asp574Asn Uncertain significance ★★ ⚠ same condition
COL4A2 p.Met1709Val Uncertain significance ★★ ⚠ same condition
COL4A2 p.Gly1158Arg Likely pathogenic ★ same condition
COL4A2 p.Ser1642Leu Uncertain significance ★ ⚠ same condition
COL4A2 c.361-1G>A Pathogenic/Likely pathogenic ★★ same type
COL4A2 p.Gly1389Arg Pathogenic/Likely pathogenic ★★ same type
COL4A2 p.Gly619Asp Likely pathogenic ★★ same type

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/col4a2-p-pro568ser (accessed [today's date]).

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